ABSTRACT:During a search for SIRT1 activators originating in nature, three new dammarane triterpenes, 6?,20(S)-dihydroxydammar-3,12-dione-24-ene (1), 6?,20(S),24(S)-trihydroxydammar-3,12-dione-25-ene (2), and 6?,20(S),25-trihydroxydammar-3,12-dione-23-ene (3), as well as two known triterpenes, dammar-20(22),24-diene-3?,6?,12?-triol (4) and 20(S)-ginsenoside Rg3 (5), were isolated from Panax ginsengleaves. Compounds 1and 3?5showed potential as SIRT1 activators, as analyzed by in vitro enzyme-based SIRT1-NAD/NADH and SIRT1-p53 luciferase cell-based assays. They were also found to increase the level of NAD+/NADH ratio in HEK293 cells. This study presents a new class of chemical entities that may be able to be developed as SIRT1 activators for antiaging and treatment of age-associated diseases.