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

BMC Complementary and Alternative Medicine

Research Article

Jongpil Kim¹  Songhee Jeon²  Hi-Joon Park³  Sora Ahn³  Jaehwan Jang⁴  Min-A Song⁴  Taek-Jin Song⁴  Sanhwa Hong⁴  Joo-Young Oh⁴  Seong-Uk Park⁵  Hye-Seoung Shin⁶  Young-Rim Jung⁷ 

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

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

DOI  :  10.1186/s12906-017-1731-2

 received in 2016-09-23, accepted in 2017-04-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAlthough 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.MethodsThe 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.ResultsKD5040 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.ConclusionsKD5040 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.

【 授权许可】

CC BY   
© The Author(s). 2017