Terpenylated coumarins as SIRT1 activators isolated from Ailanthus altissima.
Four new terpenylated coumarins (1-4) were isolated from the stem bark of Ailanthus altissima by bioactivity-guided fractionation using an in vitro SIRT1 deacetylation assay. Their structures were identified as (2'R,3'R)-7-(2',3'-dihydroxy-3',7'-dimethylocta-6'-enyloxy)-6,8-dimethoxycoumarin (1), 6,8-dimethoxy-7-(3',7'-dimethylocta-2',6'-dienyloxy)coumarin (2), (2'R,3'R,6'R)-7-(2',3'-dihydroxy-6',7'-epoxy-3',7'-dimethyloctaoxy)-6,8-dimethoxycoumarin (3), and (2'R,3'R,4'S,5'S)-6,8-dimethoxy-7-(3',7'-dimethyl-4',5'-epoxy-2'-hydroxyocta-6'-enyloxy)coumarin (4). Compounds 1-4 strongly enhanced SIRT1 activity in an in vitro SIRT1-NAD/NADH assay and an in vivo SIRT1-p53 luciferase assay. These compounds also increased the NAD-to-NADH ratio in HEK293 cells. The present results suggest that terpenylated coumarins from A. altissima have a direct stimulatory effect on SIRT1 deacetylation activity and may serve as lead molecules for the treatment of some age-related disorders.
Korea Bioactive Natural Material Bank, College of Pharmacy,  Chosun University , 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
Trong-Tuan
TT
Dao
Tien-Lam
TL
Tran
Jayeon
J
Kim
Phi-Hung
PH
Nguyen
Eun-Hee
EH
Lee
Junsoo
J
Park
Ik-Soon
IS
Jang
Won-Keun
WK
Oh
D032268:Ailanthus / Q000737:chemistry*; D000595:Amino Acid Sequence; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification*; D006801:Humans; D008156:Luciferases / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009243:NAD / Q000032:analysis / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D056910:Republic of Korea; D056564:Sirtuin 1 / Q000187:drug effects*; D013237:Stereoisomerism
D003374:Coumarins; D009243:NAD; D008156:Luciferases; D056564:Sirtuin 1