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Open Access Research article

Enhancement of catecholamine release from PC12 cells by the traditional Japanese medicine, rikkunshito

Yuko Nagamura13, Kiyoshi Terawaki24, Yasuhito Uezono2 and Toshihiko Tsukada1*

Author Affiliations

1 Division of Familial Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

2 Division of Cancer Pathophysiology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

3 Present address: JBIC Research Institute, Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo, Japan

4 Present address: Tsumura Research Laboratories, Tsumura & Co, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan

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BMC Complementary and Alternative Medicine 2014, 14:256  doi:10.1186/1472-6882-14-256

Published: 19 July 2014

Abstract

Background

Rikkunshito is a traditional Japanese herbal medicine that is used to treat appetite loss associated with cancer and other disorders. The formulation contains various constituents that influence cell signaling, and rikkunshito may accordingly affect human homeostasis through multiple regulatory pathways, including those governed by the endocrine system. We investigated the actions of rikkunshito on catecholamine release from PC12 cells, an adrenal chromaffin cell line.

Methods

The actions of rikkunshito on PC12 cells were evaluated by measuring intracellular cAMP levels, tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP) mRNA expression levels, and catecholamine levels in the culture medium. The transcriptional activation of VIP gene by rikkunshito was assessed by using a VIP promoter-driven reporter gene assay.

Results

Rikkunshito dose-dependently enhanced forskolin-induced elevations in cAMP in PC12 cells, and also increased the gene expression of TH and VIP. The transcriptional activation of VIP gene by rikkunshito was confirmed. Norepinephrine and dopamine secretion into the culture medium of PC12 cells were also dose-dependently augmented by rikkunshito and/or forskolin, but experiments with a protein kinase C (PKC) activator and a phosphodiesterase inhibitor revealed that the effects of rikkunshito were not simply due to the modulation of PKC or phosphodiesterase activity.

Conclusions

These findings suggest that rikkunshito enhances the release of catecholamines by a novel mechanism involving cAMP.

Keywords:
Rikkunshito; Catecholamine; PC12; cAMP