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BMC Complement Altern Med. 2017 Apr 19;17(1):220. doi: 10.1186/s12906-017-1731-2.

Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

Ahn S1,2, Song TJ1,3, Park SU1,4, Jeon S5, Kim J6, Oh JY1,3, Jang J1,3, Hong S1,3, Song MA1,3, Shin HS7, Jung YR8, Park HJ9,10.

Author information

1
Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.
2
Acupuncture and Meridian Science Research Centre (AMSRC), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
3
Graduate School of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
4
Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong, Seoul, 05278, Republic of Korea.
5
Dongguk University Research Institute of Bio-Medi Integration, Sangyoung-Bio, Biomedi-Campus, Dongguk-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
6
Department of Biomedical Engineering, Dongguk University, Sangyoung-Bio, Biomedi-Campus, Dongguk-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
7
SL. BIOTECH, Gasan Digital 1-ro 189, Geumcheon-gu, Seoul, 08592, Republic of Korea.
8
Seoul Pharma Laboratory, Gasan Digital 2-ro 14, Geumcheon-gu, Seoul, 08592, Republic of Korea.
9
Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea. acufind@khu.ac.kr.
10
Acupuncture and Meridian Science Research Centre (AMSRC), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. acufind@khu.ac.kr.

Abstract

BACKGROUND:

Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well.

METHODS:

The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum.

RESULTS:

KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa.

CONCLUSIONS:

KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

KEYWORDS:

Enkephalin; FosB; KD5040; L-dopa combination treatment; L-dopa-induced dyskinesia; Parkinson’s disease; Substance P; Synergic effect

PMID:
28424060
PMCID:
PMC5395961
DOI:
10.1186/s12906-017-1731-2
[Indexed for MEDLINE]
Free PMC Article

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