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

Ahn, Sora; Song, Taek-Jin; Park, Seong-Uk; Jeon, Songhee; Kim, Jong-Pil; Oh, Ju-Young; Jang, Jae-Hwan; Hong, Sanhwa; Song, Min-Young; Shin, Hye-Seoung; Jung, Young-Rim; Park, Hi-Joon

doi:10.1186/s12906-017-1731-2

Cited by 17 publications

(14 citation statements)

References 38 publications

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“…It is reported that LID influences nearly 80% of PD patients after L-DOPA treatment for 5–10 years and some of these PD patients have to stop this treatment because of serious LID (Shin et al, 2015 ). Although the lowered dose of L-DOPA is one strategy to attenuate the adverse effects induced by L-DOPA (Ahn et al, 2017 ), the efficacy could be highly decreased (Kurlan, 2005 ). Thus, to explore the combination treatment to compensate for this limitation might provide a new scenario for PD.…”

Section: Discussionmentioning

confidence: 99%

Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity

Chen

Zheng

et al. 2018

Front. Mol. Neurosci.

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Until now, the dopamine (DA) precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), remains the gold standard effective drug therapy for Parkinson’s disease (PD) patients. Nevertheless, long-term chronic L-DOPA administration leads to the drug efficacy loss and severe adverse effects, such as L-DOPA-induced dyskinesia (LID). Icariin (ICA), a flavonoid that is extracted from Epimedium, has been proved to evoke neuroprotection against DA neuronal loss in PD animal models. Here, the present study detected the effects of ICA combined with L-DOPA on 6-hydroxydopamine (6-OHDA)-elicited DA neurotoxicity and L-DOPA-induced motor dysfunction as well. PC12 cells were applied to investigate the combination treatment of ICA and L-DOPA against 6-OHDA-lesioned neurotoxicity. In addition, rat substantia nigral stereotaxic injection of 6-OHDA-induced DA neuronal injury was performed to explore the neuroprotective effects mediated by ICA combined with L-DOPA. The pathological movement triggered by L-DOPA was determined by the abnormal involuntary movements (AIM) scores analysis. In PC12 cells, ICA combined with L-DOPA produced better neuroprotection from 6-OHDA-induced neurotoxicity than ICA or L-DOPA alone treatment. In parkinsonian 6-OHDA lesioned rats, ICA conferred DA neuroprotection as monotherapy and an enhancement benefit of L-DOPA treatment after daily administration of L-DOPA and ICA for 21 days. Moreover, ICA ameliorated the development of LID as evidenced by the lowered AIM scores without affecting L-DOPA-mediated efficacy. Furtherly, ICA attenuated neuroinflammation in 6-OHDA-induced DA neuronal loss and the development of LID in vivo. In conclusion, these findings suggest ICA might be a potential promising adjuvant to enhance L-DOPA efficacy and attenuate L-DOPA-produced adverse effects in PD.

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Section: Discussionmentioning

confidence: 99%

Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity

Chen

Zheng

et al. 2018

Front. Mol. Neurosci.

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“…Several hypotheses have been proposed regarding the link between acupoint stimulation and central modulation. Previously, we suggested that local molecular signaling, such as ERK signaling, in the skin layer elicited by peripheral acupuncture stimulation may be linked with central modulation 64 . In addition, the ulnar nerve innervated around acupoints HT8 and HT7 may be associated with effects revealed in an addiction model 65 .…”

Section: Discussionmentioning

confidence: 99%

Acupuncture modulates stress response by the mTOR signaling pathway in a rat post-traumatic stress disorder model

Kim

et al. 2018

Sci Rep

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Post-traumatic stress disorder (PTSD) is a psychiatric disease that can form following exposure to a traumatic event. Acupuncture has been proposed as a beneficial treatment for PTSD, but the underlying mechanisms remain unclear. The present study investigated whether acupuncture improves depression- and anxiety-like behaviors induced using a single prolonged stress (SPS) as a PTSD rat model. In addition, we investigated whether the effects were mediated by increased mTOR activity and its downstream signaling components, which contribute to protein synthesis required for synaptic plasticity in the hippocampus. We found that acupuncture at HT8 significantly alleviated both depression- and anxiety-like behaviors induced by SPS in rats, as assessed by the forced swimming, elevated plus maze, and open field tests; this alleviation was blocked by rapamycin. The effects of acupuncture were equivalent to those exerted by fluoxetine. Acupuncture regulated protein translation in the mTOR signaling pathway and enhanced the activation of synaptic proteins, PSD95, Syn1, and GluR1 in the hippocampus. These results suggest that acupuncture exerts antidepressant and anxiolytic effects on PTSD-related symptoms by increasing protein synthesis required for synaptic plasticity via the mTOR pathway in the hippocampus. Acupuncture may be a promising treatment for patients with PTSD and play a role as an alternative PTSD treatment.

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“…Akinesia was measured as the latency in time taken to move four limbs. The test was administered as previously described (Ahn et al, 2017). The test was repeated four times for each animal.…”

Section: Methodsmentioning

confidence: 99%

“…Catalepsy was recorded as the time period for which animals retained their front legs, once placed, on a bar suspended above the floor of the test apparatus (Ahn et al, 2017). The time point at which the mice lifted their front paws from the bar marked the end of the time period.…”

Section: Methodsmentioning

confidence: 99%

“…It includes six herbs: Paeonia lactiflora root, Angelica gigas root, Bupleurum falcatum Linne root, Ligusticum chuanxiong root, Gardenia jasminoides Ellis fruit, and Paeonia suffruticosa Andrews root bark. We have previously presented evidence for the pharmaceutical effects and mechanism of action of modified CG extract and its combination with L-dopa in the MPTP-induced PD model (Ahn et al, 2017; Chang et al, 2018). Although we already demonstrated the pharmacological properties of CG on acute PD symptoms, we did not examine its effects in a chronic disease model.…”

Section: Introductionmentioning

confidence: 99%

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Gami–Chunggan Formula Prevents Motor Dysfunction in MPTP/p-Induced and A53T α-Synuclein Overexpressed Parkinson’s Disease Mouse Model Though DJ-1 and BDNF Expression

Ahn

Liu

Jang

et al. 2019

Front. Aging Neurosci.

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The Gami–Chunggan formula (GCF) is a modification of the Chunggan (CG) decoction, which has been used to treat movement disorders such as Parkinson’s disease (PD) in Traditional East Asian Medicine. To evaluate the neuroprotective effects of GCF in chronic PD animal models, we used either a 5-week treatment of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with probenecid (MPTP/p) or the α-synuclein A53T overexpressed PD mouse model. C57BL/6 mice were treated with MPTP, in combination with probenecid, for 5 weeks. GCF was administered simultaneously with MPTP injection for 38 days. The A53T α-synuclein overexpressed mice were also fed with GCF for 60 days. Using behavioral readouts and western blot analyses, it was observed that GCF prevents motor dysfunction in the MPTP/p-induced and A53T α-synuclein overexpressed mice. Moreover, GCF inhibited the reduction of dopaminergic neurons in the substantia nigra (SN) and fibers in the striatum (ST) against MPTP/p challenge. The expression of DJ-1 was increased but that of α-synuclein was decreased in the SN of PD-like brains by GCF administration. In vitro experiments also showed that GCF inhibited 6-OHDA-induced neurotoxicity in SH-SY5Y neuroblastoma cell lines and that it did so to a greater degree than CG. Furthermore, GCF induced BDNF expression through phosphorylation of Akt, ERK, CREB, and AMPK in the SN of PD-like brains. Therefore, use of the herbal medicine GCF offers a potential remedy for neurodegenerative disorders, including Parkinson’s disease.

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

Cited by 17 publications

References 38 publications

Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity

Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity

Acupuncture modulates stress response by the mTOR signaling pathway in a rat post-traumatic stress disorder model

Gami–Chunggan Formula Prevents Motor Dysfunction in MPTP/p-Induced and A53T α-Synuclein Overexpressed Parkinson’s Disease Mouse Model Though DJ-1 and BDNF Expression

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