Dammarane Triterpenes as Potential SIRT1 Activators from the Leaves of Panax ginseng

During a search for SIRT1 activators originating in nature, three new dammarane triterpenes, 6α,20­(S)-dihydroxydammar-3,12-dione-24-ene (1), 6α,20­(S),24­(S)-trihydroxydammar-3,12-dione-25-ene (2), and 6α,20­(S),25-trihydroxydammar-3,12-dione-23-ene (3), as well as two known triterpenes, dammar-20(22),24-diene-3β,6α,12β-triol (4) and 20­(S)-ginsenoside Rg₃ (5), were isolated from Panax ginseng leaves. Compounds 1 and 3–5 showed 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.