Chemical Constituents Of Lagotis Brevituba Maxim And Their Inhibitory Effects On XOD

The screening of XOD inhibitors from traditional Chinese herbal medicine with uric acid-lowering effectshas attracted much attention.Lagotis brevituba Maxim is a famous Tibetan medicine with a long history.It is one of theoriginal plants of Tibetan medicine "HongLian" with very high medicinal value,which is listed as the first of the Tibetan herbs by the Sibuyidian.Our previous study showed that the extract of Tibetan medicine L.brevituba Maxim obtained uric acid lowering effect by inhibiting XOD activity.Furthermore,it was proved that the XOD captured inhibitors in L.brevituba Maximwere composed of many kinds of chemical compositions.In this work,the uric acid lowering effects and XOD inhibitory activities were firstly investigated of different parts of the extract of L.brevituba Maxim.Then,the chemical constituents of 60% ethanol parts of the active site of the extract of the L.brevituba Maxim were isolated and identified systematically,and finally,the XOD inhibitory activities of the obtained components were studied,and the main methods and results were listed as follows:1.The potassium oxonate induced hyperuricemia mice was applied to study the uric acid lowering effects and inhibitory activity of liver XOD of different polarity fractions from L.brevituba Maxim.The results showed that the total extraction and its 60% ethanol extraction at each dose,30% ethanol extracts at high dose,90% ethanol extracts at middle and high dose exhibited uric acid lowering effects and XOD inhibitory activities.Hence,the 60% ethanol extraction was selected for further study.2.23 compounds were isolated from 60% ethanol extracts of The Lagotis brevituba Maxim by using macroporous resin,normal silica gel,ODS and pre-HPLC.And their structures were identified via NMR and MS spectroscopy.These compounds are listed as follows:Three of them were identified as flavonoids,which is luteolin(4),chrysoeriol-7-O-β-D-glucoside(5),diosmetin-7-O-β-D-glucopyranoside(6),respectively.Nine of them were identified as phenylpropanoids,which is Lagotoside H(1),methyl ferulic acid(7),3,4-dimethoxy phenylpropionic acid(8),6-O-(4-dimethoxy-(Z)-cinnamoyl)-α/β-D-glucopyranoside(9),6-O-(3,4-dimethoxy-(Z)-cinnamoyl)-α/β-D-glucopyranoside(10),Lagotoside B(11),6-O-(Z)-cinnamoyl-α/β-Dglucopyranoside(12),pinoresinol-4-O-β-D-glucopyranoside(13),syringaresinol-4’-O-β-D-monoglucoside(14),respectively.Nine of them were identified as iridoid terpenoids: They are Lagotoside C(2),Lagotoside Z(3),6-O-[α-L-(3-3,4-dimethoxycinnamoyl)-rhamnopyranosy]-catalpol(15),baldaccioside(16),globularin(17),10-O-(3,4-dimethoxy-(Z)-cinnamoyl)-catalpol(18),10-O-(3,4-dimethoxy-(E)-cinnamoyl)-catalpol(19),globularidin(20),10-O-trans-p-methoxy-(E)-cinnamoyl-catalpol(21).Two compounds were simple phenolic acids,which is 3,4-dimethoxybenzaldehyde(22),dibutyl phthalate(23),respectively.Furthermore,1,2,3 are new compounds.7,8,9,10,12,13,15,16,20,23 are first purified from genus Lagotis,while compounds 11,14,17,18,19,21,22 are isolated from Lagotis brevituba Maxim for the first time.3.The XOD inhibitory activities of 23 compounds were tested by ultraviolet spectrophotometry.The results showed that compounds 1,4,5,6,9,10 and 23 with inhibition rate from 9.7%-86.77%.Compounds 4 and 9 with inhibitory rate higher than 50% were selected to determine their IC50 values,which were 26.6 and 73.8 ugM,respectively.