Quercetin 3,5,7,3′,4′-pentamethyl ether from Kaempferia parviflora directly and effectively activates human SIRT1
Mimin Zhang, Peng Lü, Tohru Terada, Miaomiao Sui, Haruka Furuta, Kilico Iida, Yukie Katayama, Yi Lü, Ken Okamoto, Michio Suzuki, Tomiko Asakura, Kentaro Shimizu, Fumihiko Hakuno, Shin‐Ichiro Takahashi, Norimoto Shimada, Jinwei Yang, Tsutomu Ishikawa, Jin Tatsuzaki, Koji Nagata
Abstract
-dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3',4'-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety. The binding affinity between SIRT1 and Ac-p53 peptide was enhanced 8.2-fold by KPMF-8 but only 1.4-fold by resveratrol. The specific binding sites of KPMF-8 to SIRT1 were mainly localized to the helix2-turn-helix3 motif in the N-terminal domain of SIRT1. Intracellular deacetylase activity in MCF-7 cells was promoted 1.7-fold by KPMF-8 supplemented in the cell medium but only 1.2-fold by resveratrol. This work reveals that KPMF-8 activates SIRT1 more effectively than resveratrol does.