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Volume 5, Issue 5 (Suppl)

Nat Prod Chem Res

ISSN: 2329-6836 NPCR, an open access journal

Pharmacognosy 2017

July 24-25, 2017

July 24-25, 2017 Melbourne, Australia

5

th

International Conference and Exhibition on

Pharmacognosy, Phytochemistry

& Natural Products

Search for natural compounds that promote CHOP-induced apoptosis

Young Sook Yun

1

, Yukari Takeda

1

, Hiroyuki Fuchino

2

, Nobuo Kawahara

2

, Shigeru Takahashi

1

, Yuji Takahashi

1

and Hideshi Inoue

1

1

Tokyo University of Pharmacy and Life Sciences, Japan

2

Research Center for Medicinal Plant Resource, Japan

T

he transcription factor CHOP, also known as GADD 153, increases expression level and induces apoptosis in response to

endoplasmic reticulum stress caused by various factors including genetic mutation, pathogens and active oxygen. In order to

search for natural compounds that induce CHOP expression, we screened about 6,000 kinds of methanol extracts from various higher

plants and their different parts using a luciferase reporter gene assay with CHOP promoter in Mia PaCA-2 cells. In the first screening,

121 extracts showed induction of 2-fold or more luciferse activity compared to the control. By a second screening on the 121 extracts,

6 extracts showing 3-fold or more luciferase inducing activity were selected. Among them, the extract of

Macleaya cordata

(Willd.)

was separated on silica gel column chromatography and then HPLC was done. Two compounds were thereby isolated, then identified

as dihydrosanguinarine and 6-methoxydihydrosanginarine based on NMR and MS spectral data. Both compounds were found to

induce CHOP promoter-driven luciferase expression in the reporter gene assay, but did not significantly affect endogenous CHOP

protein levels. Dihydrosanguinarine increased the levels of cleaved-PARP and cleaved-caspase-3 known as apoptosis markers. This

suggests that dihydrosanguinarine may induce apoptosis not only through the ER stress pathway but also through other pathways.

Although sanguinarine was reported to be a major compound of

M. cordata

, it was not isolated in this study. This may have been due

to conversion of sanguainarine to 6-methoxysanguinarine during extraction with MeOH.

Biography

Young Sook Yun has completed her PhD from Tokyo University of Pharmacy and Life Sciences and Postdoctoral studies from Korea Institute Biosciences

and Biotechnology and National Institute of Health Science in Japan. Recently, her researches have been focused on natural chemistry related to cancer and

neurosciences.

yun@toyaku.ac.jp

Young Sook Yun et al., Nat Prod Chem Res 2017, 5:5 (Suppl)

DOI: 10.4172/2329-6836-C1-017