Investigation Of Chemical Constituents From Leaves Of Alpinia Zerumbet As Leads Of Anti-Alzheimer’s Disease

Objective: This study aims to investigate the chemical constituents of the leaves of Alpinia zerumbetand their anti-neuroinflammation effect in vitro.Methods:(Ⅰ)From the 95% ethnol extract of the leaves of A.zerumbet,constituents were separated and purified by column chromatography(silica gel,macroporus resin,MCI,and Sephadex LH-20)and their structures were elucidated by NMR,MS and comparison with the spectra data reported in the literatures.(Ⅱ)MTT and Elisa assays were used to evaluate compounds isolated for their effects on the levels of TNF-α and IL-1β in inflammatory BV2 microglia induced by Aβ.(Ⅲ)Molecular docking was adopted to understand the action mode of bioactive compounds into their potential protein target.Results:(Ⅰ)Thirteen compounds were isolated from EtOAc and n-butanol fractions from leaves of A.zerumbet and identified as Dihydro-5,6-dehydrokavain(1),Astragalin(2),Quercetin 3-O-β-D-glucoside(3),1,2-di-O-octanoyl-3-O-(6-O-α-D-galactopyranosyl-β-D-galactopyranosyl)-sn-glycer ol(4),Quercetin 3-O-β-D-glucuroside(5),Uvangoletin(6),Cardamonin(7),Yangonindimer A(8),1-p-menthene-3,6-diol(9),β-sitosterol(10),Anibadimer A(11),Lapathone(12),2’-hydroxy-4’,6’-dimethoxychalcone(13).(I)Respectively,TNF-α and IL-1β levels were downregulated by compound 7 and 13 in BV-2microglia induced by Aβ.(Ⅲ)Compounds 6,7,12 and 13 could be docked into the active pocket of BACE1 and all of the compounds binding with THR279 at 2’-OH.Conclusion:(Ⅰ)Compounds 3-5,9,and 11 are obtained from this plant for the first time.(Ⅱ)Anti-inflammatory activity of A.zerumbet is contributed by compound 7and 13 as fundamentals of anti-inflammatory substance that was preliminarily verified in this study.(Ⅲ)Aims to limitation of Aβ level and anti-neuroinflammation for treatment of AD that compound 6 and 13 could bepotential leads based on the docking and bio-assay results in frurther research after optimization of these structures.