Polygala And Studies On Chemical Constituents Of Polygala Tenuifolia Willd In South China And Its Biological Activity

"Yuan Zhi",the roots of perennial herbaceous plant—Polygala tenuifolia Willd. in Polygalaceae family,has been playing an important role as traditional Chinese medicine having bioactivities including antitussive,expectorant,antipsychotic, cognitive improving,antidote,resolutive and tonic.The pharmacological studies on Yuan Zhi indicated its effect of anti-Alzheimer's disease based on its capability of obviously ameliorating the mice memory failure reduced by scopolamine in vivo. According to the satisfying remedial practice and modern experimental results,it is extremely promising to finding leading compounds for improving cognitive ability and memory.Therefore,following the bioactive values,we investigated the chemical constituents of the active parts from the extract of Polygala tenuifolia.The roots of P. tenuifolia were refluxed in 95%ethanol and concentrated,then the residue was eluted respectively by CHCl₃,EtOAc,acetone and MeOH after mixing with silica gel.The bioactivities of four elution fractions were evaluated,as a result the MeOH portion showed the protection of PC 12 from the glutamate and serum deficiency.Bioassay-guided fractionation led to the isolation of 46 individual compounds,of which 45 were identified as 16 triterpenoid saponins,13 oligosaccharide polyesters,1 salicin,1 steroid,1 amine acid and 1 ester by spectroscopic methods including UV,IR, 1DNMR,2DNMR and MS etc as well as chemical experiments.Among them,seven triterpenoid saponins(1-7) were new and three other saponins were isolated from this plant for the first time.Some compounds and residues were evaluated in search for substances with the neuroprotection effect against glutamate and serum deficiency and the data showed the PM6EF3 and PM6EF6(fraction riched in triterpenoid saponins) portions and compounds 1-16 could protect PC12 cell from serum deficiency and glutamate at the concentration of 10^-5 mol/L,especially compounds 5,8,9,14 and 15 do better.In addition,the PM6EF3 and PM6EF6 portions exhibited moderate cognitive improving and cerebral protective effects in rats,compounds 14 and 15 also exhibited moderate cognitive improving and cerebral protective effects in rats.The ADME of gross saponins were studied and the result indicated the saponins could be absorbed into blood in its own form without any modifying.The possible structures of 10 trace saponins were deduced from the serum by use of HPLC-MS/MSⁿ.Polygala glomerata Lour.(Polygalaceae),widely distributed in the south of China including Fujian,Guangdong,Sichuan and Yunnan provinces,has traditionally been used as herbal medicine for the treatment of acute tonsillitis,tuberculosis, esophageal cancer,whooping cough,stomatitis and other inflammatory diseases such as myelitis and hepatitis pharyngitis etc.In pharmacological screen,the 95%EtOH extract showed protective effect against PC12 cell.Bioassay-guided fractionation led to the isolation 46 compounds through the combination of many isolating technologies and methods including macroporous resin column chromatography, silica gel column chromatography,Sephadex LH-20 column chromatography,mediate pressure liquid chromatography and preparative HPLC.In this thesis,41 structures were elucidated by spectroscopic and chemical methods.Among them,19 compounds were new,including a triterpenoid saponin(20),four benzophenone C-glucosides (1～4),six xanthone glucosides(5～9,18),four polygalytols(10～13) and the four remnants belonging to organic acids and asters respectively(14～17).Some compounds were evaluated particularly for their neuroprotection and anti-hepatitis considering the using characteristic of this plant in folk and the properties reported about active constituents from the Polygalaceae genus in previous literatures.Compounds 20 and 38 showed neuroprotective effects against serum deficiency and glutamate at the concentration of 10^-5mol/L.Compounds 1～8 showed heapto lprotective function against D-GaiN-induced poisoning in WB-F344 cells.On the basis of the mass spectroscopy characteristics of benzophenone C-glucosides and xanthone glucosides,the fractions containing those compounds were investigated by HPLC-MS/MSⁿ.As a result,the possible structures of sixteen trace compounds were deduced,in which five were new compounds.