Toki-to protects dopaminergic neurons in the substantia nigra from neurotoxicity of MPTP in mice

Risa Sakai, Yoshifumi Irie, Takeshi Murata, Atsushi Ishige, Naoko Anjiki, Kenji Watanabe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Parkinson's disease (PD) is a neurodegenerative disease of the brain characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). No clinically proven drugs that may halt or retard the progression of PD have been reported. This study examined the anti-PD effect of a traditional Japanese/Chinese herbal remedy Toki-to (TKT) using mice treated with a neurotoxin 1-methy 1-4-pheny 1-1,2,3,6-tetrahydroxypyridine (MPTP). TKT showed improvement of MPTP-induced PD-like symptoms (bradykinesia) in a behavioral test (pole test). Histological studies of SNs from these mice demonstrated that TKT had a protective effect on dopaminergic neurons against MPTP neurotoxicity. Real-time RT-PCR analyses of mRNA from SNs demonstrated that expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) genes were decreased by MPTP treatment and that these decreases were reversed by TKT administration prior to MPTP treatment. DNA microarray analyses indicated that TKT per se suppressed gene expression of serum-and glucocorticoid regulated kinase (SGK) that is believed to be a molecule that drives the pathogenesis of PD. Hence, it is suggested that TKT may inhibit the activation of SGK at the transcriptional level and thusmay participate in halting the progression of MPTP-induced neurotoxicity.

Original languageEnglish
Pages (from-to)868-873
Number of pages6
JournalPhytotherapy Research
Volume21
Issue number9
DOIs
Publication statusPublished - 2007 Sep

Fingerprint

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopaminergic Neurons
Substantia Nigra
Neurons
Parkinson Disease
Neurodegenerative diseases
Hypokinesia
Dopamine Plasma Membrane Transport Proteins
Neurotoxins
Tyrosine 3-Monooxygenase
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
Gene expression
Neurodegenerative Diseases
Real-Time Polymerase Chain Reaction
Poles
Brain
Genes
Chemical activation

Keywords

  • MPTP
  • Parkinson's disease
  • Pole test
  • Serum and glucocorticoid- regulated kinase (SGK)
  • Toki-to

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Sakai, R., Irie, Y., Murata, T., Ishige, A., Anjiki, N., & Watanabe, K. (2007). Toki-to protects dopaminergic neurons in the substantia nigra from neurotoxicity of MPTP in mice. Phytotherapy Research, 21(9), 868-873. https://doi.org/10.1002/ptr.2172

Toki-to protects dopaminergic neurons in the substantia nigra from neurotoxicity of MPTP in mice. / Sakai, Risa; Irie, Yoshifumi; Murata, Takeshi; Ishige, Atsushi; Anjiki, Naoko; Watanabe, Kenji.

In: Phytotherapy Research, Vol. 21, No. 9, 09.2007, p. 868-873.

Research output: Contribution to journalArticle

Sakai, R, Irie, Y, Murata, T, Ishige, A, Anjiki, N & Watanabe, K 2007, 'Toki-to protects dopaminergic neurons in the substantia nigra from neurotoxicity of MPTP in mice', Phytotherapy Research, vol. 21, no. 9, pp. 868-873. https://doi.org/10.1002/ptr.2172
Sakai, Risa ; Irie, Yoshifumi ; Murata, Takeshi ; Ishige, Atsushi ; Anjiki, Naoko ; Watanabe, Kenji. / Toki-to protects dopaminergic neurons in the substantia nigra from neurotoxicity of MPTP in mice. In: Phytotherapy Research. 2007 ; Vol. 21, No. 9. pp. 868-873.
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