构树黄酮类化合物及其PTP1B抑制活性研究
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摘要
利用正相和反相硅胶柱色谱、凝胶柱色谱和反相高效液相等分离和纯化方法,从构树Broussonetia papyrifera茎枝中分离得到11个黄酮类化合物。运用NMR,MS,UV,IR等波谱方法鉴定了它们的结构,分别为构树素A(1),5,7,3',4'-四羟基-3-甲氧基-8-香叶基黄酮(2),8-异戊烯基槲皮素-3-甲醚(3),构树醇D(4),构树黄酮醇B(5),新乌尔醇(6),构树醇E(7),8-(1,1-二甲基丙烯基)-5'-(3-甲基-2-丁烯基)-3',4',5,7-四羟基黄酮醇(8),构树黄酮醇E(9),4,2',4'-三羟基查尔酮(10),紫铆花素(11)。其中化合物1为新的异戊烯基取代的黄酮醇,化合物3,6,10,11为首次从构属植物中分离得到,化合物4和7为首次从构树中分离得到。化合物1～5和7～9具有显著的蛋白酪氨酸磷酸酶1B抑制活性,IC50为(0.83±0.30)～(4.66±0.83)μmol·L-1。
Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) μmol·L-1.
Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) μmol·L-1.
引文
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[2]中国药典.一部[S].2015.
[3]江苏新医学院.中药大辞典[M].上海:上海人民出版社,1977.
[4]Wang G W,Huang B K,Qin L P.The genus Broussonetia:a review of its phytochemistry and pharmacology[J].Phytother Res,2012,26(1):1.
[5]Tsai F H,Lien J C,Lin L W,et al.Protective effect of Broussonetia papyrifera against hydrogen peroxide-induced oxidative stress in SH-SY5Y cells[J].Biosci Biotech Bio,2009,73(9):1933.
[6]Kim H S,Lim J,Lee D Y,et al.Kazinol C from Broussonetia kazinoki activates AMP-activated protein kinase to induce antitumorigenic effects in HT-29 colon cancer cells[J].Oncol Rep,2015,33(1):223.
[7]朱开梅,陈丹,李美波,等.构树叶总黄酮调控Bcl-2与Bax蛋白表达及caspase-3活性诱导HepG-2细胞凋亡的研究[J].中国实验方剂学杂志,2014,20(19):128.
[8]Kwak W J,Moon T C,Lin C X,et al.Papyriflavonol A from Broussonetia papyrifera inhibits the passive cutaneous anaphylaxis reaction and has a secretory phospholipase A2-inhibitory activity[J].Biol Pharm Bull,2003,26(3):299.
[9]朱开梅,刘建楠,顾生玖,等.构树药用活性化学成分及药理临床应用研究进展[J].中国实验方剂学杂志,2011,17(1):198.
[10]Ryu H W,Lee B W,Curtislong M J,et al.Polyphenols from Broussonetia papyrifera displaying potentα-glucosidase inhibition[J].J Agr Food Chem,2010,58(1):202.
[11]Chen R M,Hu L H,An T Y,et al.Natural PTP1B inhibitors from Broussonetia papyrifera[J].Bioorg Med Chem Lett,2002,12(23):3387.
[12]Goldstein B J,Bittner-Kowalczyk A,White M F,et al.Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B:possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein[J].J Biol Chem,2000,275(6):4283.
[13]Huang Q H,Lei C,Wang P P,et al.Isoprenylated phenolic compounds with PTP1B inhibition from Morus alba[J].Fitoterapia,2017,122:138.
[14]Wang M,Gao L X,Wang J,et al.Diels-Alder adducts with PTP1B inhibition from Morus notabilis[J].Phytochemistry,2015,109:140.
[15]Wang M,Yu B W,Yu M H,et al.New isoprenylated phenolic compounds from Morus laevigata[J].Chem Biodivers,2015,12(6):937.
[16]Wu L Q,Lei C,Gao L X,et al.Isoprenylated flavonoids with PTP1B inhibition from Ficus tikoua[J].Nat Prod Commun,2015,10(12):2105.
[17]Guo F,Feng L,Huang C,et al.Prenylflavone derivatives from Broussonetia papyrifera,inhibit the growth of breast cancer cells in vitro and in vivo[J].Phytochem Lett,2013,6(3):331.
[18]尚明英,王庆辉,肖军军,等.新的异戊烯基黄酮类化合物及其应用:中国,ZL201110197701.5[P].2012.
[19]Zhang P C,Wang S,Wu Y,et al.Five new diprenylated flavonols from the leaves of Broussonetia kazinoki[J].J Nat Prod,2001,64(9):1206.
[20]Matsumoto J,Fujimoto T,Takino C,et al.Components of Broussonetia papyrifera(L.)Vent.I.Structures of two new isoprenylated flavonols and two chalcone derivatives[J].Chem Pharm Bull,2008,33(8):3250.
[21]Zheng Z P,Cheng K W,Chao J,et al.Tyrosinase inhibitors from paper mulberry(Broussonetia papyrifera)[J].Food Chem,2008,106(2):529.
[22]Chen R M,Hu L H,An T Y,et al.Natural PTP1B inhibitors from Broussonetia papyrifera[J].Bioorg Med Chem Lett,2002,12(23):3387.
[23]Fang S C,Shieh B J,Wu R R,et al.Isoprenylated flavonols of formosan Broussonetia papyrifera[J].Phytochemistry,1995,38(2):535.
[24]Veitch N C,Sutton P S E,Kite G C,et al.Six new isoflavones and a 5-deoxyflavonol glycoside from the leaves of Ateleia herbertsmithii[J].J Nat Prod,2003,66(2):210.
[25]Prachayasittikul S,Buraparuangsang P,Worachartcheewan A,et al.Antimicrobial and antioxidative activities of bioactive constituents from Hydnophytum formicarum Jack[J].Molecules,2008,13(4):904.
[26]Shi L,Yu H P,Zhou Y Y,et al.Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening[J].Acta Pharmacol Sin,2008,29(2):278.