An Integrative Approach to Treat Parkinson's Disease: Ukgansan Complements L-Dopa by Ameliorating Dopaminergic Neuronal Damage and L-Dopa-Induced Dyskinesia in Mice

Huh, Eugene; Choi, Jin Gyu; Sim, Yeomoon; Oh, Myung Sook

doi:10.3389/fnagi.2018.00431

Cited by 10 publications

(14 citation statements)

References 31 publications

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“…Intrastriatal injection of 6-OHDA was performed for each mouse based on the methods described in a previous study ( Huh et al, 2018 ). Essentially, each mouse was anesthetized with tribromoethanol followed by a unilateral injection of 2 μl vehicle (saline with 0.1% ascorbic acid for sham-operated mice) or 16 μg of 6-OHDA in 2 μl vehicle into the target region (coordinates with respect to bregma in mm: AP 0.5, ML 2.0, DV−3.0), according to the stereotaxic atlas of mouse brain ( Franklin, 2013 ) on a stereotaxic apparatus (myNeuroLab, St. Louis, MO, United States).…”

Section: Methodsmentioning

confidence: 99%

DA-9805, a Herbal Mixture, Restores Motor Manifestations in 6-Hydroxydopamine-induced Parkinson’s Disease Mouse Model by Regulating Striatal Dopamine and Acetylcholine Levels

et al. 2022

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Loss of dopamine (DA) is one of the primary features of Parkinson’s disease (PD); however, imbalances of non-dopaminergic neurotransmitters significantly contribute to the disabilities noted in advanced PD patients. DA-9805 is the ethanolic extraction of the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), the root of Angelica dahurica (Hoffm.) Benth. and Hook.f. ex Franch. and Sav. (Apiaceae) and the root of Bupleurum falcatum L. (Apiaceae), which have been widely utilized as an enhancer of motor function in East Asia. This study aimed to investigate whether DA-9805 modified motor dysfunctions and imbalances associated with DA and other neurotransmitters in a 6-hydroxydopamine-induced PD mouse. We confirmed the expressions of proteins related with neurotransmissions in the striatum. In addition, we measured the striatal neurotransmitters using HPLC and analyzed their correlation. DA-9805 significantly improved motor impairments and restored the altered levels of neurotransmitters in the striatum. Moreover, DA-9805 improved the altered expressions of tyrosine hydroxylase (TH), DA transporter, and choline acetyltransferase (ChAT) in the ipsilateral part of mouse striatum or SNpc, which implies the neuroprotection. We also found that the level of striatal acetylcholine (Ach) has the moderate negative correlation with motor functions and TH expression in the SNpc. This study indicates that DA-9805 restores motor dysfunctions by normalizing the increased levels of striatal Ach via modulating DA transmission and ChAT expressions as well as its neuroprotective effects.

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Section: Methodsmentioning

confidence: 99%

DA-9805, a Herbal Mixture, Restores Motor Manifestations in 6-Hydroxydopamine-induced Parkinson’s Disease Mouse Model by Regulating Striatal Dopamine and Acetylcholine Levels

et al. 2022

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“…In addition, it was confirmed that the TH level in Nurr1 siRNA-infected cells statistically significantly reduced the effect of Ukgansan. However, experimental results show that the Ukgansan does not regulate dopamine cells by utilizing only the activity of Nurr1, but also by activating other mechanisms, and related reports have been reported on various mechanisms [11][12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Ukgansan (Yi-Gan san in China or Yokukansan in Japan), is a traditional herbal medicine that first appeared in "Bao Ying Cuo Yao," and has been observed to have therapeutic effects on neurodegenerative diseases such as PD and behavioral and psychological symptoms of dementia (BPSD) in various dementias such as Alzheimer's disease (AD), dementia with Lewy bodies (LBD) and frontotemporal dementia (FTD) [10][11][12][13][14]. According to a retrospective study using data for 5 years conducted at a Korean medicine hospital in South Korea, herbal medicine modified with Ukgansan is the most frequently used to improve the motor symptoms of PD patients [15].…”

Section: Introductionmentioning

confidence: 99%

Ukgansan Protects Dopaminergic Neurons against MPTP-Induced Neurotoxicity via the Nurr1 Signaling Pathway

Chae

Jang

Seol，In-Chan

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor that protects dopaminergic neurons and is a promising therapeutic target for Parkinson’s disease (PD). Parkinson’s disease is a neurodegenerative disorder caused by the destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and the long-term use of conventional dopamine replacement therapies causes many side effects, highlighting the need for new treatments such as complementary and alternative medicine. Ukgansan has been used in East Asia to treat neurological disorders, including neurodegenerative diseases, and has been reported to have strong effects in treating patients with PD. In addition, recent studies have reported that Ukgansan has a neuroprotective potential. However, there are no detailed studies on the mechanism of action of Nurr1. Thus, unlike previous studies, we focused on the Nurr1 pathways. We confirmed neurotoxicity and apoptosis signaling in the differentiated PC12 cells. In addition, to confirm the protective effect of Ukgansan, we conducted behavioral tests (motor coordination and postural balance, and bradykinesia) and tyrosine hydroxylase immunohistochemistry in both the SNpc and striatum. Specifically, this study demonstrated the effect of Ukgansan in protecting dopaminergic neurons and increasing Nurr1 involved in maintaining dopamine levels by activating Nurr1 expression in MPTP-induced PC12 cells and a mouse model of PD. In this mechanism, the loss of dopaminergic neurons and dopamine depletion were suppressed, and motor impairment caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity was improved. These results provide evidence that Ukgansan ameliorates PD’s motor symptoms and progression.

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“…These findings confirmed the critical limitations of L-DOPA since its effects were merely symptomatic and not as fundamental. In addition, one such limitation concerned that L-DOPA might accelerate DA neuronal loss during the progression of PD [27]. Moreover, pre-treatment and co-treatment of ASA with L-DOPA still generated DA neuroprotection and ameliorated LID without affecting the therapeutic actions of L-DOPA, suggesting that ASA might be repurposed as an adjunct treatment to mitigate LID in PD therapy.…”

Section: Discussionmentioning

confidence: 99%

Aspirin attenuates L-DOPA-induced dyskinesia in hemi-parkinsonian rats

Zhu¹,

Zheng²,

Li³

et al. 2020

Preprint

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Background: At present, L-DOPA remained the gold standard therapy for motor symptoms of Parkinson’s disease (PD) patients. However, prolonged administration of L-DOPA led to the development of dyskinesia. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), had been widely used to relieve pain and inflammation. Recent studies indicated aspirin produced neuroprotection against dopamine (DA) neuronal loss in animal model. This study aimed to explore the effects of aspirin pre-treatment and co-treatment with L-DOPA on DA neurotoxicity and L-DOPA-induced dyskinesia (LID) as well.Methods: Rats received a single 6-hydroxydopamine (6-OHDA) injection into substantia nigra to induce DA neuronal loss. For aspirin pre-treatment before L-DOPA studies: One day after 6-OHDA stimulation, rats were daily administrated with aspirin for 3 weeks followed by daily L-DOPA treatment along with aspirin for additional 3 weeks. For aspirin co-treatment with L-DOPA studies: Three weeks after 6-OHDA administration, rats were daily treated by L-DOPA together with aspirin for another 3 weeks. DA neurotoxicity was analyzed via rat PD-like behavior test and DA neuronal counting. The movement disorders of dyskinesia triggered by L-DOPA were determined by the abnormal involuntary movements (AIM) scores analysis.Results: we demonstrated both aspirin pre-treatment and co-treatment exerted anti-LID effects during L-DOPA treatment on 6-OHDA-lesioned rats. In addition, aspirin not only ameliorated DA neuronal damage, but also reduced the development of dyskinesia without affecting L-DOPA efficacy. Furtherly, inhibition of glial cells activation and the subsequent neuroinflammatory response might be involved in aspirin-attenuated dyskinesia.Conclusion: the present study suggested aspirin could have beneficial potential to attenuate LID in PD.

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An Integrative Approach to Treat Parkinson's Disease: Ukgansan Complements L-Dopa by Ameliorating Dopaminergic Neuronal Damage and L-Dopa-Induced Dyskinesia in Mice

Cited by 10 publications

References 31 publications

DA-9805, a Herbal Mixture, Restores Motor Manifestations in 6-Hydroxydopamine-induced Parkinson’s Disease Mouse Model by Regulating Striatal Dopamine and Acetylcholine Levels

DA-9805, a Herbal Mixture, Restores Motor Manifestations in 6-Hydroxydopamine-induced Parkinson’s Disease Mouse Model by Regulating Striatal Dopamine and Acetylcholine Levels

Ukgansan Protects Dopaminergic Neurons against MPTP-Induced Neurotoxicity via the Nurr1 Signaling Pathway

Aspirin attenuates L-DOPA-induced dyskinesia in hemi-parkinsonian rats

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