Yokukansan, a kampo medicine, protects PC12 cells from glutamate-induced death by augmenting gene expression of cystine/glutamate antiporter system Xc-

Hitomi Kanno; Zenji Kawakami; Kazushige Mizoguchi; Yasushi Ikarashi; Yoshio Kase

doi:10.1371/journal.pone.0116275

Yokukansan, a kampo medicine, protects PC12 cells from glutamate-induced death by augmenting gene expression of cystine/glutamate antiporter system Xc-

PLoS One. 2014 Dec 31;9(12):e116275. doi: 10.1371/journal.pone.0116275. eCollection 2014.

Authors

Hitomi Kanno¹, Zenji Kawakami¹, Kazushige Mizoguchi¹, Yasushi Ikarashi¹, Yoshio Kase¹

Affiliation

¹ Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Inashiki, Ibaraki, Japan.

Abstract

Effects of the kampo medicine yokukansan on gene expression of the cystine/glutamate antiporter system Xc-, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc- subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids / pharmacology
Amino Acid Transport Systems, Acidic / genetics*
Animals
Cell Death / drug effects
Drug Evaluation, Preclinical / methods
Drugs, Chinese Herbal / chemistry
Drugs, Chinese Herbal / pharmacology*
Fusion Regulatory Protein 1, Heavy Chain / genetics
Gene Expression Regulation / drug effects
Glutamates / pharmacology*
Glutathione / metabolism
Indole Alkaloids / pharmacology
Medicine, Kampo
PC12 Cells / drug effects*
Protective Agents / pharmacology
Rats

Substances

Alkaloids
Amino Acid Transport Systems, Acidic
Drugs, Chinese Herbal
Fusion Regulatory Protein 1, Heavy Chain
Glutamates
Indole Alkaloids
Protective Agents
Yi-Gan San
geissoschizine methylether
xCT protein, rat
hirsuteine
Glutathione
hirsutine

Grants and funding

This study was funded by Tsumura & Co. The funder provided support in the form of salaries for all authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.