Chemical And Bioactive Studies On Glycyrrhiza Uralensis Fisch.

Glycyrrhiza uralensis Fisch.,Glycyrrhiza glabra L.and Glycyrrhiza inflata Bat.,three species belonging to the same Genus,are listed under the item of licorice in Chinese Pharmacopoeia.The dried root and rhizome of these three kinds of plants are all used as important Chinese herbs for the treatment of deficiency of spleen and stomach,fatigue,cough,palpitations and also for detoxification.G.uralensis is the most widely used and planted species of licorice.Previous phytochemical investigations indicated that flavonoids,triterpenoid saponins,coumarins and stilbenoids are the major constituents of G.uralensis,more specifically,prenylated flavonoids and coumarins are characteristic constituents obtained from G.uralensis,this suggested that G.uralensis is a good resource for prenylated compounds.This study performed a systematic phytochemical study on the root and rhizome of G.uralensis,and also examined the bioactivities of some compounds.By using silica gel column chromatography,MCI column chromatography,C18 reverse phase silica gel column chromatography,Sephadex LH-20 gel column chromatography and semi preparative HPLC,44 compounds were obtained from the ethanol reflux extract of G.uralensis.The structures of all of the 44 compounds were determined by NMR,MS,UV,IR,CD and other spectroscopic techniques.They are idenfied as two new compounds and 42 known compounds.The two new compounds are liquiritcoumarin(1),belonging to coumarin;and crotoliquiritin(2),belonging to dihydroflavone glycoside;42 known compounds include 16 isoflavones:ononin(3),barpisoflavone A(4),gliricidin(5),ammopiptanoside A(6),daidzein(7),formononetin(8),orobol(9),licoisoflavone A(10),glycyrrhisoflavone(11),genistein(12),wistin(13),licoricone(14),licoisoflavone B(15),gancaonin G(16),isoangustone A(17)and sissotrin(18);6 dihydroflavonoids:liquiritin(19),liquiritin apioside(20),liquiritigenin-7-O-?-D-apiofuranosyl-4'-O-?-D-glucopyranoside(21),liquiritigenin(22),naringenin(23)and glabrol(24);2 dihydroisoflavones:licoisoflavanone(25)and glisoflavanone(26);2 flavonoids:7,4'-dihydroxyflavone(27)and licoflavone(28);5 flavonols:isolicoflavonol(29),licoflavnol(30),kaempferol(31),7,4'-dihydroxyflavonol(32)and kumatakenin(33),5 chalcones:tetrahydromethoxychalcone(34),isoliquiritigenin(35),2',4',3,4,a-pentahydroxychalcone(36),licochalcone B(37)and butein(38),3 coumarins:hedysarimcoumestan B(39),glycyrol(40)and glycyrin(41);1 pterocarpoid:medicarpin-3-O-glucoside(42);one stilbene:gancaonin I(43);1 other kinds of compounds:4-prenylphenol(44).By using MTT assay,the antiproliferation effect of some of the isolated compounds were evaluated,the results showed that the compounds 8,15,16,24,25,29,35,37,40 possess moderate cytotoxic activities.Screened by using a stable cell line transfected with luciferase,compounds 1 and 2 were identified to be potential Nrf2 pathway activators.Further tests including immunoblot and immunofluorescence assay demonstrated that 1 and 2 are indeed Nrf2 pathway inducers.