Anti-apoptotic effect of modified Chunsimyeolda-tang, a traditional Korean herbal formula, on MPTP-induced neuronal cell death in a Parkinson's disease mouse model.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

The modified-Chungsimyeolda-tang (DG) is an important traditional Korean herbal formula used in traditional oriental medicine for treatment of cerebrovascular disorders, including stroke. The formula is based on the book "Dongui Sasang Shinpyun".

AIM OF THE STUDY:

In the previous studies, the neuroprotective effect of DG is demonstrated in an in vitro Parkinson's disease (PD) model, and in this study, the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD is used to evaluate the behavioral effect of DG and possible mechanism through anti-apoptosis of DG. 6-Hydroxydopamine (6-OHDA) also is used to evaluate the anti-apoptosis effect of DG in SH-SY5Y cells.

MATERIALS AND METHODS:

MPTP was used to evaluate the behavioral damage and neurotoxicity in mice. The bradykinesia symptom was measured by a Pole test and a Rota-rod test in mice. Also the loss of tyrosine hydroxylase (TH)-positive neurons induced by MPTP was examined by an immunohistochemical assay. The DG-mediated anti-apoptosis effect was measured using an immunoblotting assay with apoptosis-related markers such as Bax and cleaved caspase-3. DG and 1-methyl-4-phenylpyridinium (MPP(+)) were co-treated with primary dopaminergic neurons to evaluate the protective effect of DG. The expression of caspase-3 and PARP was measured to detect the protective effect of DG from the damage by 6-OHDA.

RESULTS AND CONCLUSIONS:

The treatment with DG resulted in prophylactic effects on MPTP-induced Parkinsonian bradykinesia and the immunohistochemical analysis showed that DG provided the neuroprotection against the MPP(+)-induced dopaminergic neurons loss through the anti-apoptosis effect. The present results suggested that it might be possible to use DG for the prevention of substantia nigra pars compacta (SNpc) degeneration induced by exposure to the toxic substances, such as MPTP/MPP(+), in PD mouse model.

• Authors: Huan Li, Gunhyuk Park, Nayoung Bae, Joonki Kim, Myung Sook Oh, Hyun Ok Yang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 176 Pg. 336-44 (Dec 24 2015) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 26593210 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antiparkinson Agents
• Bax protein, mouse
• Neuroprotective Agents
• Neurotoxins
• Plant Extracts
• bcl-2-Associated X Protein
• chungsimyeolda-tang
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Caspase 3

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Antiparkinson Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Behavior, Animal (drug effects)
• Brain (cytology, drug effects, metabolism)
• Caspase 3 (metabolism)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cells, Cultured
• Disease Models, Animal
• Dopaminergic Neurons (drug effects)
• Humans
• Korea
• Male
• Medicine, Traditional
• Mice, Inbred C57BL
• Neuroprotective Agents (pharmacology, therapeutic use)
• Neurotoxins
• Parkinson Disease (drug therapy, metabolism)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Rats, Sprague-Dawley
• bcl-2-Associated X Protein (metabolism)