Open Access Highly Accessed Research article

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

Yuzo Nakagawa-Yagi1*, Yukiko Sato2, Emi Matsumoto3, Shin-ichi Nakatsuka3, Tsuyoshi Sakaki4, Yukiko Muramatsu1, Takaaki Hara1 and Toshiro Aigaki2

Author Affiliations

1 Hakuju Institute for Health Science Co. Ltd, 37-5, Tomigaya 1-chome, Shibuya-ku, Tokyo, 151-0063, Japan

2 Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo, 192-0397, Japan

3 Nagara Science Co. Ltd, 479-15 Nagase, Oritate, Gifu, 501-1132, Japan

4 National Institute of Advanced Industrial Science and Technology (AIST) Kyushu, 807-1 Shuku-machi, Tosu, Saga, 841-0052, Japan

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BMC Complementary and Alternative Medicine 2012, 12:101  doi:10.1186/1472-6882-12-101

Published: 18 July 2012

Abstract

Background

Extracts of Sasa senanensis Rehder are used in traditional Japanese medicine; however, little is known about the underlying mechanisms of their potential health benefits.

Methods

S. 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.

Results

PA 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.

Conclusions

Our 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.

Keywords:
Drosophila; Histone demethylase; Lifespan extension; Traditional Japanese medicine