Research On The Material Basis And Mechanism For Hypouricemia And Anti-BPH Of Tibetan Medicine Of Urtica Hyperborea Jacq.ex Wedd.

[Research background and purpose]Urtica hyperborea Jacq.ex Wedd.is Urtica perennial herband widely distributed in southern Tibet to northern,Qinghai,Gansu,Sichuan,Xinjiang,and so on,“Sazhen”(Sazhu,Sazhumu,Tibetan name is.)is a common Tibetan medicine.“Ministerial standard of Tibetan medicine”notes two species nettle,there are U.laetevirens Maxim and U.fissa Pritz,they use dry ground section.And the Tibetan medicine monograph records that U.hyperborea Jacq.ex Wedd.is equivalent to a variety of nettle also used as "Sazhen".its role is clearing heat,clearing damp,improvingstomach temperature,antihypertension,relieve convulsion and spasmolysis.Internal treatment for rheumatic fever,"long" disease,stomach cold,dyspepsia,rheumatic pain,hypertension,postpartum cramps,children cramps,urticarial.According to the pharmacy and pharmacology researches of medicinal plant of Urtica,there are flavonoids,alkaloids,lignans,coumarin,terpenoids,organic acids,volatile oil and steroidal constituents,It has more activities,for example,anti-inflammatory,analgesic and anti rheumatism,and anti BPH,antibacterial activity,antioxidant,regulating blood lipids,hypoglycemic,and so on.New drugs have been developed from Urtica and marked in Europe.U.hyperborea is rich in resources,but it has modern pharmacy and pharmacology reports not been seen so far.According to the clinical application of Tibetan medicine and related research literature,explore the mechanism and material basis of U.hyperborea hypouricemia and anti-benign prostatic hyperplasia.[Research mothods and results]The following results were obtained:1.Study on the effect of difference extract of U.hyperborea on hypoururicemia(1)The effects of expression uric acid transporter URAT1 and OAT1 protein on HK2 cells in different extraction of U.hyperborea were observed in vitro.The results showed that the high-and low-dose group of ethyl acetate extraction,the high dose of n-butanol fraction and the high-andlow-dose of alcohol-soluble fraction had significant down-regulation of URAT1 and up-regulation of OAT1 protein expression.But different extraction of U.hyperborea have not inhabition XOD activity in vitro.(2)Using animal models of hyperuricemia in vivo,by measuring serum UA,Cr,BUN levels,liver XOD and serum ADA activity,and renal urate transporter m RNA expression,the results showed that compared with themodel,all of extracts of U.hyperborean has significantly reduced serum UA levels,and the AG fraction had a significant effect on lowering serum UA levels,at the same time,reducing Cr and BUN levels,inhibiting liver XOD and serum ADA activity,and down-regulating kidneys.The role of uric acid transporter URAT1 m RNA and up-regulation of OAT1 m RNA expression suggests that the alcohol-soluble fraction not only inhibits liver XOD activity,but also reduces the production of xanthine and hypoxanthine by inhibiting serum ADA activity,by reducing uric acid production.In addition,this site also has the function of protecting the kidneys.2.Study on the effect of difference extracts of U.hyperborea on benign prostatic hyperplasiaUsing prostate hyperplasia mice model,we investigated the prostate index,serum DHT and EGF levels,prostate tissue EGF and Bcl-2 m RNA expression,and prostate histopathology.The results showed that compared with model,ethyl acetate fractionand the alcohol-soluble fraction has a significant effect of lowering the prostate index,and at the same time,it can lower the serum DHT,EGF levels and down-regulate the expression of EGF and Bcl-2 m RNA in the prostate tissue,and can also be seen from the pathological sections of the prostate tissue of the two fractions,some glands and glandular cells showed no hyperplasia,neatly arranged,and a few glands and cells appeared hyperplasia with less secretion.Overall,the degree of benign prostatic hyperplasia was significantly reduced.3.Basic research on hypouricemic and anti-BPH substances in U.hyperboreaIn this paper,36 compounds were identified from U.hyperborea,among which 30 were identified by UPLC-Q-TOP-MS/MS,and 13 conponents were compared with the control;From the ethyl acetate fraction(anti-BPH effect)16 compounds were identified,7 were compared with the control;22 compounds were identified from the alcohol-soluble fraction,and 8 were compared with the control.6 known compounds were isolated by systematic chemical separation.Among them,there were 11 components in the ethyl acetate fraction and the alcohol-soluble fraction.The above compounds include 8 flavonoids,14 phenolic compounds,8 phenylpropanoids(4 coumarins,4 lignans),and 1 terpenoid compound.All of the above compounds were identified from this plant for the first time.And the 2 components have down-regulated URAT1 and up-regulated OAT1 protein,we were determined that Isofraxoside and Vicenin-2 are active ingredients for hypoururicemia.[Conculusion]From the above experimental results,it can be concluded that U.hyperborea has the effect of reducing uric acid and anti-BPH.The effective fraction of hypouricemic is the alcohol-soluble fraction,and the effective fraction of anti-BPH is the ethyl acetate fraction and the alcohol-soluble fraction.Its alcohol-soluble fraction has both hypouricemic and anti-BPH effects.The mechanism of hypouricemicin alcohol-soluble fraction may be to maintain the uric acid normal level in hyperuricemia model mice body by inhibiting liver XOD and serum ADA activity or by regulating renal urate transporter URAT1 and OAT1 gene and protein expression.Through in vitro cell experiments,it was determined that the 2 components isolated from this fraction may be the active component of hypouricemic.The anti-BPH mechanism of ethyl acetate fraction and alcohol-soluble fraction may be through down-regulation of EGF m RNA expression,reduction of serum DHT levels,inhibition of prostate cell hyperproliferation,or down-regulation of inhibitory Bcl-2m RNA expression to promoted apoptosis.After reviewing relevant literatures at domestic and foreign,flavonoids,lignans and coumarins have anti-BPH effects.Flavonoids,lignans,coumarins and other components,it can be inferred that these types of compounds may be their anti-BPH basis meterials.