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-Yagi,Shin-Ichi Nakatsuka,Takaaki Hara,Yukiko Sato,Emi Matsumoto,Tsuyoshi Sakaki,Toshiro Aigaki,Yukiko Muramatsu

doi:10.1186/1472-6882-12-101

Abstract

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.

Highlights

Extracts of Sasa senanensis Rehder are used in traditional Japanese medicine; little is known about the underlying mechanisms of their potential health benefits
The fruit fly Drosophila melanogaster has been widely used in aging research, because of the extensive knowledge of its biological pathways, which are conserved in other organisms including humans
Fraction 4 was identified as having antioxidant activity, as its superoxide anion radical scavenging activities (SOSA) measurement was relatively high (Figure 1A); it was further fractionated by high-performance liquid chromatography (HPLC) to obtain fraction 4-II, which had the highest activity of all the fractions (Figure 1B)

Summary

Introduction

Extracts of Sasa senanensis Rehder are used in traditional Japanese medicine; little is known about the underlying mechanisms of their potential health benefits. Polyphenols are widely found in natural products [1], and have generated much interest because of the health benefits derived from their antioxidant activities as free-radical scavengers [2]. Leaves from the bamboo genus Sasa are known to have anti-microbial, antiallergic and anti-invasion properties, and have been used in Japanese traditional medicine for treating. The current study isolated a small-molecule antioxidant with superoxide anion radical scavenging activities (SOSA) from subcritical water extracts of S. senanensis leaves, and identified the small molecule as 3,4-dihydroxybenzaldehyde (protocatechuic aldehyde or PA). We screened the biological activity of PA in the current context, and examined its effects on the lifespan of Drosophila

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Conclusion