Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of Sasa senanensis leaves prolongs the lifespan of Drosophila melanogaster

BMC Complementary and Alternative Medicine

Research Article

Yukiko Sato¹  Toshiro Aigaki¹  Yuzo Nakagawa-Yagi²  Takaaki Hara²  Yukiko Muramatsu²  Emi Matsumoto³  Shin-ichi Nakatsuka³  Tsuyoshi Sakaki⁴ 

[1] Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, 192-0397, Hachioji, Tokyo, Japan;Hakuju Institute for Health Science Co. Ltd, 37-5, Tomigaya 1-chome, 151-0063, Shibuya-ku, Tokyo, Japan;Nagara Science Co. Ltd, 479-15 Nagase, 501-1132, Oritate, Gifu, Japan;National Institute of Advanced Industrial Science and Technology (AIST) Kyushu, 807-1 Shuku-machi, 841-0052, Tosu, Saga, Japan;

关键词: Drosophila;    Histone demethylase;    Lifespan extension;    Traditional Japanese medicine;   

DOI  :  10.1186/1472-6882-12-101

 received in 2011-12-20, accepted in 2012-07-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundExtracts of Sasa senanensis Rehder are used in traditional Japanese medicine; however, little is known about the underlying mechanisms of their potential health benefits.MethodsS. senanensis leaves were extracted with subcritical water. An active small-molecule was isolated using reversed-phase high-performance liquid chromatography (HPLC), and identified as 3,4-dihydroxybenzaldehyde (protocatechuic aldehyde or PA). The effects of PA on the activity of histone demethylase, the Drosophila melanogaster lifespan and gene expression in Drosophila S2 cells were investigated.ResultsPA inhibited the activity of Jumonji domain-containing protein 2A (JMJD2A) histone demethylase in a dose-dependent manner with a half-maximal inhibitory concentration (IC50) of 11.6 μM. However, there was no effect on lysine-specific demethylase 1 (LSD1), histone deacetylase 1 (HDAC1) or HDAC8. PA significantly extended the lifespan of female, but not male, Drosophila. In Drosophila S2 cells, the eukaryotic translation initiation factor 4E binding protein (4E-BP) was up-regulated by PA exposure.ConclusionsOur findings provide insight into the possible relationship between the pharmacological modulation of histone demethylation and lifespan extension by PA; they might also be important in the development of alternative therapies for age-related disorders.

【 授权许可】

CC BY   
© Nakagawa-Yagi et al.; 2012