Terpenylated coumarins as SIRT1 activators isolated from Ailanthus altissima

TY - JOUR

T1 - Terpenylated coumarins as SIRT1 activators isolated from Ailanthus altissima

AU - Dao, Trong-Tuan

AU - Tran, Tien-Lam

AU - Kim, Jayeon

AU - Nguyen, Phi-Hung

AU - Lee, Eun-Hee

AU - Park, Junsoo

AU - Jang, Ik-Soon

AU - Oh, Won-Keun

PY - 2012/7/27

Y1 - 2012/7/27

N2 - 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.

AB - 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.

KW - Ailanthus

KW - Amino Acid Sequence

KW - Coumarins

KW - Humans

KW - Luciferases

KW - Molecular Structure

KW - NAD

KW - Nuclear Magnetic Resonance, Biomolecular

KW - Plant Bark

KW - Plant Stems

KW - Republic of Korea

KW - Sirtuin 1

KW - Stereoisomerism

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1021/np300258u

DO - 10.1021/np300258u

M3 - Journal article

C2 - 22799262

SN - 0163-3864

VL - 75

SP - 1332

EP - 1338

JO - Journal of Natural Products

JF - Journal of Natural Products

IS - 7

ER -