| Diabetes mellitus(DM)is a chronic disease with a rather complex mechanism,characterized by persistent hyperglycemia in the body.At present,DM has become one of the three major diseases in the world,and its incidence and patients are still rising year by year.According to IDF's 2017 Global Diabetes Development Survey,the number of diabetic patients worldwide has reached 424 million,while this number is close to 114 million in China.Diabetes is mainly divided into two major categories,type 1 diabetes and type 2 diabetes,and more than 90% of patients are type 2 diabetes mellitus(T2DM).One of the main pathological features of T2 DM is insulin resistance(IR).Researchs have shown that relieving IR in peripheral tissues will be benefical for treatment of T2 DM.Glucose transporter 4(GLUT4)is one of the most important glucose transporters in the body and is the major glucose transporter in the liver,muscle,and adipose tissue.Many studies have shown that increasing expression and translocation of GLUT4 will help alleviate IR symptoms in T2 DM.Therefore,the study of how to increase the expression and translocation of GLUT4 protein may become an important breakthrough point in the study of diabetes.GLUT4 is considered to be one of the potential therapeutic targets for the treatment of T2 DM.Based on biological activity-oriented,the present research was focused on the effective fractions of one medicinal fungus and two ethnic drugs using phytochemical experimental methods.A variety of chromatographic and spectroscopic methods have been used for purification,separation,and structural identification.And pharmacological experimental analyses for monomeric compounds were also conducted.The purpose is to find natural products with biological activity or novel structures.Finally,60 compounds were isolated and identified.These compounds are structurally diverse and include flavonoids,pyrones,coumarins,phenylpropanoids,aromatics,alkaloids,and flavonoid glycosides,including five new compounds.In addition,the screening for the antidiabetic activity and anticancer activity of some monomeric compounds was completed.The polyphenol-rich fractions of Phellinus igniarius Quel.(PI-PRE)exhibited significantly antidiabetic activity in vivo and in vitro.Ten compounds were isolated from the PI-PRE fraction,including six aromatic compounds,3,4-dihydroxy-benzalacetone(1),2,4-dihydroxybenzoic acid(3),gentisaldehyde(4),3,4-dihydroxybenzoic acid(5),4-(1-hydroxypropan-2-yl)naphthalene-1,6-dicarboxylic acid(8),6,8,9-trihydroxy-3-methyl-3,4-dihydro-1H-benzo[h] isochromen-1-one(9),in which compounds 8 and 9 were new compounds.One coumarin compound was identified as 7,8-dihydroxycoumarin(2).One flavone compound was identified as 7,3'-dihydroxy-5'-methoxyisoflavone(6).Two pyrone compounds were identified as phelligridins A(7)and inoscavin C(10).We performed a GLUT4 translocation assay against PI-PRE and 4 compounds(2,1,6,10).The bioassay results showed that the PI-PRE fraction exhibited good effects on GLUT4 translocation by 1.33 folds,and compounds 6 and 10 exhibited good effects on GLUT4 translocation by 1.62 and 1.87 folds,respectively.The ethyl acetate fraction of Sophora tonkinensis Gagnep.(ST-EtOAc)exhibited significantly antidiabetic activity in vivo and in vitro.Eighteen compounds were isolated from ST-EtOAc,including 5 pterocarpus,four isoflavone,three flavonoles,and five dihydroflavones as well as one flavanonol.Five Pterocarpus were identified as 1-hydroxy-4-isoprenyl-maackiain(11),trifolinhizin(16),trifolinhizin-6'-monoacetate(17),maackiain(18)and medicarpin(24),in which compound 11 is a new compound.Four isoflavone compounds were identified as genistein-7-O-?-D-glucose(12),ononin(13),formononetin(14)and genistein(15).Three flavonol compounds were identified as quercetin(19),6,8-diprenylkaempferol(20)and dehydrolupinifolinol(25).Five dihydroflavones were identified as 7,4'-dihydroxy-6,8-diprenylfavanone(21),glabrol(22),sophoranone(23),sophoranochromene(26),and 2-(2',4'-dihydroxyphenyl)-8,8–dime(3-methyl-2-butenyl)-8H-pyrano [2,3-d]chroman-4-one(17).One flavanonol was identified as Lespeflorins B4(28).Thirteen compounds(21,16-27)were screened with a GLUT4 translocation assay,and the results showed that compounds 17-23 and 25-27 containing isopentene side chains exhibited good effects on GLUT4 translocation by 1.35-2.75 folds,of which the most active compound sophoranone(23)enhance GLUT4 translocation by 2.75 fold.Subsequently,a dose-response relationship experiment was performed on the compound 23 and it exerted the strongest GLUT4 translocation activity at the concentration of 10 ?M.Finally,computer molecular modeling experiments were performed on these flavonoids containing isopentenyl side chains.The experimental results showed that the presence of isopentenyl groups in the compounds can better fill the hydrophobic pocket of GLUT4,especially the isopentenyl groups substituted in C-8 or C-5'.The acidic ethyl acetate fraction,the alkaline ethyl acetate fraction and the n-butanol fraction of Sophora alopecuroides L.exhibited significantly anti-diabetic activity in vitro experiments.Totally,thirty-two compounds were isolated from three active fractions of S.alopecuroides.Twenty-two compounds were isolated from the acidic ethyl acetate fraction,including seven phenolic acids,piscidic acid(29),methyl 2-(4-hydroxybenzyl)tartrate,ethyl 2-(4-hydroxybenzyl)tartrate(31),methyl eucomate(32),2-(4-hydroxybenzyl)malic acid(33),ethyl 2-(4-hydroxybenzyl)malic acid(34)and p-hydroxybenzoic acid(49),in which compounds 30 and 34 were new compounds.Three phenylpropanoids compounds were identified as caffeic acid(35),ferulic acid(36),and ethyl caffeate(50).Three chalcones compounds were identified as butein-4-O-?-D-glucose(37),iso-liquiritigenin(38)and butein(39).Two flavonoids compounds were identified as hydroxygenkwanin(40)and 7,3',4'-trihydroxylflavone(41).Six isoflavones compounds were identified as 7,3'-dihydroxy-5'-methoxy-isoflavone(42),7,3',4'-trihydr-oxyisoflavone(43),daidzein(44),3',4'-dihydroxy-isoflavone-7-O-?-D-glucose(45),pseudobaptigenin(46),and rothindin(47).One flavanone compound was identified as butin(48).Seven compounds were isolated from the alkaline ethyl acetate fraction,including five matrine alkaloids,sophoridine(51),(-)-13,14-dehydro sophoridine(52),oxymatrine(53),sophocarpine(54)and sophocarpidine(55).Two quinolizidine alkaloids were identified as N-methylcytisine(56)and(-)-epibaptifoline(57).Three compounds were isolated from the n-butanol fraction,in which two phenylpropanoids compounds were identified as 4-glucosyloxy-3-methoxy(58)and glucosyl methyl ferulate(60),and one flavonoid glycoside compound was identified as luteolin-4'-O-?-D-glucose(59). |
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