Licochalcone B (LCB), an extract from the root of Glycyrrhiza inflate, has the same caffeic acid scaffold as curcumin (Cur), which is known as an anti-Alzheimer's disease (AD) agent. However, there is no relevant research about anti-AD activity of LCB. In this study, the anti-AD activity of LCB was investigated. LCB could inhibit amyloid beta (A beta(42)) self-aggregation (IC50 = 2.16 +/- 0.24 mu M) and disaggregate pre-formed A beta(42) fibrils, reduce metal-induced A beta(42) aggregation through chelating metal ions. Molecular docking further revealed that LCB inhibited A beta(42) self-aggregation through forming two hydrogen bonds with Lys28 to block the salt bridge interaction at the C-terminus of A beta(42). Anti-oxidant property of LCB was also observed by DCFH-DA assay. In addition, LCB did show neuroprotective activity against H2O2-induced cell death in SH-SY5Y cells. In general, our results demonstrate that LCB, as a multifunctional agent, is likely to be promising therapeutics for AD. [GRAPHICS] .