Studies On The Chemical Constituents Of Aquilaria Sninesis And Elaeocarpus Dubius

Neurodegenerative diseases seriously endanger human health.Currently,there are only a few therapeutic drugs,and they can only provide relief.Therefore,the development of new drugs against neurodegenerative diseases is very necessary.In the previous study,we found that agarotetrol,the main component of Aquilaria sinensis,promoted neuron-like differentiation of PC12 cells,while Elaeocarpus dubius extract showed inhibitory activity on acetylcholinesterase.This prompted us to isolate and screen the neuroprotective active components from A.sinensis and E.dubius.In this thesis,the chemical components of the heartwood(Agarwood)and the branches of Elaeocarpus dubius were separated by chromatographic techniques.The structure of the compounds was identified by spectral techniques.The neuroprotective activity of the isolated compounds was evaluated.Seventeen compounds were isolated and identified from A.sninesis.These compounds include one spirolactone,aquilarisinolide(1);five sesquiterpenoids,(2R,4S,5R,7R)-2-hydroxyeremophila-9,11-dien-8-one(2),(1R,4S,5S,7R,11R)-13-hydroxyepidaphnauran-9-en-8-one(3),(4R,5S,7R,8S,10 S,13R)-8,13-dihydroxyrotunda-1,11-dien-3-one(4),daphnauranol A(5)and daphnauranol B(6);seven 2-(2-phenethyl)chromones,5,6-dihydroxy-2-(2-phenylethyl)chromone(7),2-(2-phenylethyl)chromone(8),6-methoxy-2-(2-phenylethyl)chromone(9),6-methoxy-2-[2-(3-methoxyphenyl)ethyl]chromone(10),6,7-dimethoxy-2-(2-phenylethyl)chromone(11),6,7-dimethoxy-2-[2-(3-methoxyphenyl)ethyl]chromone(12)and 6,7-dimethoxy-2-[2-(4-methoxybenzenyl)ethyl]chromone(13);two 5,6,7,8-tetrahydro-2-(2-phenethyl)chromones,isoagarotetrol(14)and 8-chloro-2-(2-phenethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydrochromone(15);two diphenylpentanones,1-hydroxy-1,5-diphenylpentan-3-one(16)and 3-hydroxy-1,5-diphenylpentan-1-one(17).Among them,compounds 1-4 were new compounds,compounds 16 and 17 were new natural products,and compounds 6 and 7 were isolated from this species for the first time.At a concentration of 10 μM,compounds 1-11,14 and 17 showed weak proproliferative activities of PC12 cells with differentiation rates between 3.95% and 6.45%.The BACE1-inhibitory activities of all tested compounds were very weak with less than 30% inhibition at a concentration of 20 μM.At a concentration of 20 μM,compounds 4,6-7,10,14 and 16 showed significant protective effects on corticosterone-induced injury in PC12 cells(P <0.001),while compounds 3 and 11 showed weak protective effects(P <0.05).At a concentration of 20 μM,compound 14 showed a significant protective effect on MPP-induced injury in PC12 cells(P <0.001);compound 4 showed a moderate protective effect on MPP-induced injury in PC12 cells(P <0.01);compound 16 showed a weak protective effect on MPP-induced injury in PC12 cells(P <0.05).Fourteen compounds were isolated and identified from E.dubius.These compound include four triterpenoids,elaeocarpudoside A(18),elaeocarpudoside B(19),cucurbitacin D(20)and cucurbitacin F(21);five benzoic derivatives,2-hydroxybenzoic acid(22),3,4-dihydroxybenzoic acid(23),gallic acid(24),ethyl 3,4,5-trihydroxybenzoate(25)and methyl 2-O-β-D-glucopyranosyloxybenzoate(26);two ellagic derivatives,3-O-methylellagic acid-4?-O-α-3?-O-acetylrhamnopyranoside(27),3-O-methyl ellagic acid-4?-O-β-4?-O-acetylrhamnopyranoside(28);three phenylpropanoids,salaciacochinoside A(29),methyl 3-O-caffeoylquinate(30)and methyl 5-O-caffeoylquinate(31).Among them,compound 18 was a new compound,while compound 29 was a new natural product;all compounds were isolated from this species for the first time.Screening for PC12 cell differentiation activity screening revealed that compounds 26 and 29-30 showed weak activities at a concentration of 10 μM,the differentiation rates were 4.93%,5.64% and 4.33%,respectively.The BACE1-inhibitory activities of all tested compounds were very weak with less than 30% inhibition at a concentration of 20 μM.At a concentration of 20 μM,Compounds 27 and 29 showed significant protective effects on corticosterone-induced injury in PC12 cells(P <0.001).All test compounds did not show significant protective effect on MPP-induced injury in PC12 cells at a concentration of 20 μM(the concentration of compounds 20 and 21 was 2 μM)(P > 0.05).Screening of acetylcholinesterase inhibitor activity revealed that compounds 21,24 and 27 showed very weak activities at a concentration of 50 μM,the inhibition rates were 12.84%,11.33% and 12.11%,respectively.