Studies On The Active Constituents As Inhibitors Of Beta Secretase From Homalomena Gigantea And Aloe Arborescens

β-secretase(BACE) is a new target related to the pathogenis and progress of Alzheimer's disease(AD). Since 1990, more and more attention has been focused on the research of the BACE inhibitors.Homalomena gigantea Engl., belonging to the Araceae family, is mainly distributed in southwestern regions of China. In our previous studies we found some aromatic derivatives with long fatty chain shown prominent BACE inhibitory activity fom Homalomena occulta. In the course of our search for compounds with the same skeleton and other different BACE inhibitors, the 95％ethanol extract from Homalomena gigantea Engl. was studied. TLC-directed and bioassay-guided fractionations of Homalomena gigantea Engl. resulted in the isolation of 14 compounds, and they were identified as 24-methylenecycloartan-3β-ol(1), cycloeucalenol (2), sitgmast-5-en-3β-stearate(3), sitgmast-5-en-3β-linoleate(4), stigamast4-en-3-one(5), stigamast-4, 22-dien-3-one(6),β-sitosterol(7), daucosterol(8), (6'-O-palmitoyl)-sitosterol-3-O-β-D-glucoside(9), cis, trans-2, 5-Dimethylcyclopentanol(10), 1-O-stearoyl-2-O-linoleylpropane and/or 1-O-linoleyl-2-O-stearoyl propane(11), stearic acid(12), 6-methoycalopogonium isoflavone A(13), 1-O-β-D-glucopyranoyl(2S, 3R, 4E, 8Z)-2-[(2(R)-hydroxyicosanoyl)amido]-4, 8-octadecadiene-1, 3-diol(14)。All of these compounds were isolated from Homalomena gigantea Engl. for the first time.Aloe arboreseens(Liliaceae family) is a Japanese traditional herb that has long been used for the treatment of various diseases. Withβ-secretase as the active target, we have isolated a bioactive chromone derivative(AV-4) from Aloe vera L. In order to search for more chromone derivatives and other different BACE inhibitors, the 95％ethanol extract of A. arborescens was fractionated with the help of UV-spectroscopy and bioassay, and 11 compounds were isolated. On the basis of various spectroscopic analysis and chemical methods, they were identified as 6'-O-isobutyryl aloenin A (15), aloenin A (16), p-coumaroyl aloenin (17), feruloyl aloenin (18), 7-O-methylaloeresin A (19), (E)-2-acetonyl-8-(2'-O-feruloxyl)-β-D-gluco-pyranosyl-7-methoxy-5-methyl-chromone (20), aloe-emodin (21), barbaloin A (22), elgonica-dimer A (23), elgonica-dimer B (24), 6'-O-acetyl barbaloin (25), respectively. Among them, 15 is a new aloenin derivative.The BACE inhibitory activities of these compounds were evaluated. Compound 3, 10, 17, 18, 19 and 22 showed less activity. A mixture of 5 and 6 showed medium activity. No other compound showed BACE inhibitory activitie.