Studies On Chemical Constituents Of Aspidopterys Obcordata Hemsl.

ObjectivePhosphdiesterases(PDEs)include 11 isozymes(PDEI to PDE11),They can regulate gene expression and nucleotide signaling pathway through the hydrolysis of phosphodiester bonds of 3',5' cyclic adenosine and guanosine monophosphate(cAMP and cGMP).PDE4 is a critical regulator of their intracellular concentrations and their biological effects.Recently,PDE4 inhibitor plays an important role in the treatment of arthritis,chronic obstructive pulmonary disease(COPD)and exerts neuroprotective role in a range of central nervous system insults including spinal cord and Alzheimer's disease.Natural products have been one of the most important resources of novel lead compounds especially for the treatment of neurodegenerative diseases.Therefore,researchers are focus on the PDE4 inhibitor that derive from the traditional herb medicine,which have been high-efficiency,low-toxicity and selectively.Aspidopterys obcordata Hemsl.,a wood liana belonging to the Malpighiaceae family,is mainly distributed in Hainan and Yunnan province.The Aspidopterys obcordata Hemsl.has been used for the treatment of urinary infections,cystitis,rheumatic bone pain.The preliminary study of this subject found that the 95%EtOH extract had a certain degree of PDE4 inhibitory effect.Under the guidance of PDE4 inhibitory activity,we studied the chemical constituents of the EtOAc extract and n-BuOH extract.In order to find the PDE4 inhibitory compounds and provide a reference for the further development and utilization of this plant.MethodsThis paper is to study the constituents of Aspidopterys obcordata Hemsl.based on the PDE4 inhibitory activity of EtOAc and n-BuOH extracts,the constituents were isolated by repeated chromatography with silica gel,Sephadex LH-20,ODS columns and semi-preparing liquid chromatography.Their structure were elucidated by spectroscopic analysis(IR?UV?NMR?MS?CD et al.).The bioassay in vitro torwards PDE4 was prsormed via[3H]tag liquid scintillation counting method.ResultsThe 95%EtOH crude extract and the EtOAc and n-BuOH extracts of A.obcord ate.were evaluated for their inhibitory activities against PDE4,when the concentract ion of the EtOAc and n-BuOH extracts was at lmg/mL,the inhibition rate of EtO Ac and n-BuOH extracts against PDE4 were 7.13%and 62.4%,respectively.Twenty-nine compounds which include nine phenylpropanoid(1.5?21?23?24?25?27?28?39),three sponins(3?6?13),one triterpenoid(26),two phenolic a cids(2?4),nine phenol derivatives(8?10?11?14?15?16?17?20?22);four al kaloids(9?12?18?19)and one flavone(7).They were obtained and identified as N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(1),3,4-dihydroxybenzoic aci d(2),Stigmastane-3?,6a-diol(3),3,4-Dihydroxyphenyl acetate(4),Lyoniresinol(5),Daucosterol(6),Catechin(7),3,4-dihydroxybenzoic acid-3-O-?-L-rhamnoside(8),2-(?-D-glucopyranosylosy)-3-isoxazolin-5-one(9),Cinnacasolide C(10),2,6-dimethoxy-4-O-?-D-glucopyranoside(11),Allantoin(12),?-sitosterol(13),2,4,6-trimethoxyphenyl-1-O-iS-D-glucopyranoside(14),3,4-dihydroxybenzoic acid-4-O-?-L-glucopyranoside(15),2,6-dimethoxy-4-hydroxy-1-O-?-D-glucopyranoside(16),1,2,4-trimethoxyphenyl-1-O-?-L-rhamnoside(17),1-?-D-rifuranosy-1,2,4-triazole(18),Uridine(19),Rhyncoside C(20),Dihydroelentheroside B(21),1-(?-L-rhaonosyl(1-6)-?-D-glucopyranosylosy)-3,4,5-trimethoxybenzene(22),4-O-(glycer-2-yl)?dihydroconiferyl alcohol-1'-O-?-D-manno pyranoside(23),4-O-(glycer-2-yl)-dihydrocomferyl alcohol-1'-O-?-D-mannopyranoside(24),Lyoniresinol-4-O-?-glucoside(25),(6R,9S)-3-O-?-ionol apiofuranosylglucopy-rano side(26),Lyoniresinol-4-O-?-L-rhamnosyl-9'-O-?-D-glucopyranoside(27),Lyonside(28),Nudiposide(29).We used[3H]tag liquid scintillation counting method to get PDE4 inhibitor activity of 13 compounds in vitro test.The results showed that compound 7 have a significant inhibitory activity against PDE4,with inhibitory rate of 90%at 10 ?M.The other compunds(4?5?8?10?12?14?15?18?19?25?28?29)also showed different inhibitory activity against PDE4.ConclusionExcept for the compounds 3?6 and 13,the other compounds were isolated from Aspidopterys obcordata Hemsl.for the first time.The compounds 8?15?17?27 are new compounds.The inhibitory activity test showed that compound 7 has a significant inhibitoryactivity against PDE4,with inhibitory rate of 90%at 10 ?M.