AMP-activated protein kinase (AMPK) has been proposed as a therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. The bioassay-guided fractionation of an EtOAc-soluble extract of the stem bark of Erythrina abyssinica led to the isolation of a new coumestan, erythribyssin N (1), and two new benzofurans, erythribyssin F (2) and erythribyssin H (3), along with five known compounds (4-8). When tested for their stimulatory effects on AMPK activity at a concentration of 10 muM, compounds 4 and 5 showed potent activation, while compounds 1, 2, and 7 had moderate effects. These results suggest that benzofurans and coumestans may be new lead compounds for regulating the AMPK enzyme.