Anti- Hyperuricemia Consitituents Based On The Targets Of Xanthine Oxidase In Clinopodium Chinensis And Rabdosia Excise

Hyperuricemia is characterized as a state of high blood uric acid（UA）,it results from overproduction and/or underexcretion of UA in the body.It regarded as an important risk factor for gout.It associated with cardiovascular disease such as hypertension,angiocardiopathy,kidney and disease diabetes.There are two different kinds drugs for hyperuricemia aim to promoting uric acid excretion or restrain uric acid synthesis.Xanthine oxidase inhibitor acting on the key enzymes of xanthine oxidase aim to restrain uric acid synthesis.Due to its allergic reaction and the toxic side effects such as liver and kidney the application of it has limited by a certain extent,so far it has become a hot research to explore effective,nontoxic,clear constituent for uric acid at home and abroad.Our teames researched the inhibition of 41 extracts from the 10 medicinal plants in changbai Mountain on xanthine oxidase.Then founded that the ethyl acetate extract of Clinopodium chinensis and Rabdosia excise exhibited a strong inhibitory activity against XO,but didn’t see the reports on this two plants of the inhibitory effect on xanthine oxidase.On the basis of it we begain to research the inhibitory effect of Clinopodium chinensis and Rabdosia excise on xanthine oxidase.The effective parts of Clinopodium chinensis and Rabdosia excise were subjected to activity-guided fraction on an CC on Lobar Li Chroprep RP-18.After separation processes by preparative HPLC of active fractions,ten compounds were obtained from Clinopodiumchinensisandtheirstructurewereidentifiedaseriocitrin（1）,naringenin-7-O-rutinoside（2）,apigenin-7-O-rutinoside（3）,didymin（4）,naringenin（5）,ethyl rosmarinate（6）,acacetin-7-O-rutinoside（7）,buddlejasaponin IV（8）,clinoposide II（9）,clinoposaponins XI（10）.Sixteen compounds were obtained from R.excise,and their structure were identifieas 3,4-dihydroxyphenacyl alcohol（1）,protocatechuic acid（2）,caffeic acid（3）,pedalitin（4）,rabdokunmin C（5）,excisanin A（6）,kamebakaurin（7）,glaucocalyxin A（8）,glaucocalyxin B（9）,2α,3β,19α-thihydroxy-28-norus-12-ene（10）,2α,3β,24-trihydroxy-olean-12-en-28-oicacid（11）,hyptadienicacid（12）,2α,3α-dihydroxyurs-12-en-28-oic acid（13）,3-epimaslinic acid（14）,maslinic acid（15）,oleanic acid（16）.Compounds 10 and 11 are firstly isolated from the genus of Isondon.The compounds isolated from the ethyl acetate extract of Clinopodium chinensis didn’t exhibited a strong inhibitory activity against XO.According to the Chou-Talalay combination index analysis to analyze the interaction effects and dose-effect of different compoundsandtheircombination.Thenfindedthatthecombinationof didymin-naringenin and didymin-ethyl rosmarinate showed a significant synergistic at the rate of 1:1.The inhibition of xanthine oxidase increased from 0.1 to 0.9 and the effects of the different CI values are less than 1（CI>1 antagonism,CI=1 additive effect,CI<1synergism）.Diterpenoids isolated from the ethyl acetate extract of and Rabdosia excise didn’t showed strong active on XO.The compounds of protocatechuic acid,caffeic acid and pedalitin showed strong active on XO,the IC₅₀ of protocatechuic acid,caffeic acid pedalitin are 139.7,122.3,18.4μΜrespectily.This topic researched the chemical composition of the ethyl acetate extract of the Clinopodium chinensis and Rabdosia excise,and research the inhibitory effect of the compounds isolated from Clinopodium chinensis and Rabdosia excise on xanthine oxidase in vitro,provide a scientific basis for the comprehensive development and utilization of Clinopodium chinensis and Rabdosia excise based on the targets of xanthine oxidase,and has important academic value and application prospect.