Jpn. J. Pharmacol. 86 (2), 183-188 (2001)

Long Term Effects of Toki-shakuyaku-san on Brain Dopamine and Nerve Growth Factor in Olfactory-Bulb-Lesioned Mice

Qing-Hua Song1,2, Kazuo Toriizuka1,3, Guang-Bi Jin1, Takeshi Yabe1 and Jong-Chol Cyong2,*

1The Research Division, Oriental Medicine Research Center, The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan
2Department of Bioregulatory Function, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
3Laboratory of Pharmacognosy & Phytochemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

*Corresponding author. FAX: +81-3-3818-4754, E-mail:

Abstract: We used olfactory-bulb-lesioned mice induced by intranasal irrigation with zinc sulfate as a model of dementia, to investigate the effects of Toki-shakuyaku-san (TSS) on monoamines and nerve growth factor (NGF) in brain regions. TSS was given daily through the drinking water for either 1, 2, 3, 4 or 8 weeks from the day after olfactory lesion. The administration of TSS significantly suppressed the decrease of 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in olfactory bulb of olfactory-lesioned mice at 1 week, and tended to suppress the decrease of DOPAC and HVA during the experimental session. However, the administration of TSS had no influence on dopamine contents. NGF contents in the olfactory bulb were increased after the irrigation, and the value returned to the same level as the control at 8 weeks after. Although the NGF contents in the olfactory bulb of TSS-treated mice were immediately increased at 1 and 2 weeks, the value returned to normal level within 3 weeks. These findings indicate that oral administration of TSS prevents the reduction of dopamine metabolites, DOPAC and HVA, and immediately increased NGF contents in the olfactory bulb. This suggested that TSS treatment promotes the NGF contents in olfactory nerves and rescue the neurons from damage.

Keywords: Kampo medicine, Dopamine, Nerve growth factor, Olfactory bulb, Toki-shakuyaku-san
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