6-Shogaol, an Active Ingredient of Ginger, Improves Intestinal and Brain Abnormalities in Proteus Mirabilis-Induced Parkinson’s Disease Mouse Model

Huh Eugene,Choi Jin Gyu,Choi Yujin,Ju In Gyoung,Noh Dongjin,Shin Dong-yun,Kim Dong Hyun,Park Hi-Joon,Oh Myung Sook 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.4

Parkinson’s disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

Pathological effect of gut microbe-derived metabolite on parkinson disease

Eugene Huh,Jin Gyu Choi,In Gyoung Ju,Yujin Choi,Myung Sook Oh 한국실험동물학회 2020 한국실험동물학회 학술발표대회 논문집 Vol.2020 No.7

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

( Eugene Huh ),( Hyo Geun Kim ),( Hanbyeol Park ),( Min Seo Kang ),( Bongyong Lee ),( Myung Sook Oh ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.3

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Ab) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Ab induced neurotoxicity. In mice with Ab-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 mg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

Highly selective CD44-specific gold nanorods for photothermal ablation of tumorigenic subpopulations generated in MCF7 mammospheres

Lee, Eugene,Hong, Yoochan,Choi, Jihye,Haam, Seungjoo,Suh, Jin-Suck,Huh, Yong-Min,Yang, Jaemoon IOP Pub 2012 Nanotechnology Vol.23 No.46

<P>Heterogeneous stem-like populations within tumor tissues are the primary suspects in causing cancer recurrence and malignancy. It is essential to selectively kill these tumorigenic populations. We created a novel system for photothermally ablating specific cells from three-dimensional mammospheres. A CD44-positive subpopulation, with tumorigenic and self-renewal potential, spontaneously arises in MCF7 breast cancer cell-engineered mammospheres. Using anti-CD44 antibody-linked gold nanorods, which strongly absorb near infrared light and increase local temperature, we effectively targeted and photo-ablated atypical cells. This biomarker-specific photothermal ablation model, using a smart nanoplatform, is a promising new strategy for selectively killing cancer cells, while sparing normal tissues. </P>

Development of a diagnostic method for Parkinson's disease by reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection

Oh, Minhwa,Huh, Eugene,Oh, Myung Sook,Jeong, Ji-Seon,Hong, Seon-Pyo Elsevier 2018 Journal of Pharmaceutical and Biomedical Analysis Vol.153 No.-

<P><B>Abstract</B></P> <P>We developed a diagnostic method for Parkinson's disease by simultaneously analyzing biogenic amines and their metabolites using reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection (RP-HPLC-IPAD) method. Dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and homovanillic acid (HVA) were used as biomarkers to diagnose Parkinson's disease. All target components were detected with good sensitivity using sodium hydroxide (as a post-column eluent). The limit of detection (S<B>/</B>N <B>=</B> 3) and limit of quantification (S<B>/</B>N <B>=</B> 10) of the target components ranged from 0.020 to 2.400 ng and from 0.080 to 8.000 ng, respectively. The coefficients of linear regression ranged from 0.9996 to 1.0000, all inter-day and intra-day precision values were <3.43%, and the average recovery and RSD ranged from 97.55 to 103.60% and 0.22 to 4.79% for mice striatum samples. This method exhibited good selectivity, sensitivity, and reproducibility and can be used directly without any pretreatment steps. Our method will be useful as a tool to diagnose Parkinson’s disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed a diagnostic method for PD by simultaneously analyzing biogenic amines and their metabolites using RP-HPLC-IPAD method. </LI> <LI> This novel RP-HPLC-IPAD method for detecting biogenic amines and their metabolites is reported here for the first time. </LI> <LI> Dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and homovanillic acid (HVA) were used as biomarkers to diagnose PD. </LI> <LI> The striatum tissues of mice brains were analyzed within 20 minutes with good accuracy, precision, and sensitivity for all biomarkers. </LI> <LI> This method is a novel approach to analyzing biogenic amines and their metabolites, and will be useful as a tool to diagnose PD. </LI> </UL> </P>

Ukgansan protects dopaminergic neurons from 6-hydroxydopamine neurotoxicity via activation of the nuclear factor (erythroid-derived 2)-like 2 factor signaling pathway

Eo, Hyeyoon,Huh, Eugene,Sim, Yeomoon,Oh, Myung Sook Elsevier 2019 Neurochemistry International Vol.122 No.-

<P><B>Abstract</B></P> <P>The sustenance of redox homeostasis in brain is the crucial factor to treat Parkinson's disease (PD). Nuclear factor (erythroid-derived 2)-like 2 factor (Nrf2)-mediated antioxidant response is well known for the main cellular endogenous defense mechanisms against oxidative stress. This study investigated for the first time the effects and possible mechanisms of action of Ukgansan on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in both <I>in vitro</I> and <I>in vivo</I> models of PD. We investigated the protective effect of Ukgansan against 6-OHDA with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. In addition, we demonstrated that Ukgansan significantly increased the expression of antioxidant response elements (ARE) and pro-survival protein as Bcl2 and suppressed the expression of pro-apoptotic factors, such as Bax, cytochrome <I>c</I>, and caspase-3 using immunoblotting. For the <I>in vivo</I> study, we used a mouse model of PD involving stereotaxic injection of 6-OHDA into the striatum (ST). Ukgansan alleviated motor dysfunctions induced by 6-OHDA followed by pole, open-field, and rotation tests. Dopaminergic neuronal loss and Nrf2 activation were evaluated by immunohistochemistry in the mouse ST and substantia nigra pars compacta (SNpc) regions. Ukgansan significantly protected dopaminergic neurons from 6-OHDA toxicity in mouse ST and SNpc by activating Nrf2. These results indicate that Ukgansan inhibited 6-OHDA-induced dopaminergic neuronal cell damage via activation of Nrf2 and its related factors in 6-OHDA-induced dopaminergic loss <I>in vitro</I> and <I>in vivo</I>. Thus, Ukgansan might delay the progression of PD via maintenance of redox homeostasis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> UGS promotes the antioxidant defense system via activating Nrf2 against 6-OHDA. </LI> <LI> Nrf2 activation induces the cell survival signaling pathway in dopaminergic neurons. </LI> <LI> UGS protects the dopaminergic neuron against 6-OHDA in <I>in vitro</I> and <I>in vivo</I> systems. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson’s Disease

Choi Yujin,Huh Eugene,Lee Seungmin,Kim Jin Hee,Park Myoung Gyu,Seo Seung-Yong,Kim Sun Yeou,Oh Myung Sook 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.4

Long-term administration of levodopa (L-DOPA) to patients with Parkinson’s disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

Injury-stimulated Sonic hedgehog expression in microglia contributes to neuroinflammatory response in the MPTP model of Parkinson's disease

Lee, Jeong Hwi,Chung, Young Cheul,Bok, Eugene,Lee, Hankyu,Huh, Sue Hee,Lee, Ji Eun,Jin, Byung Kwan,Ko, Hyuk Wan Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration.</P> <P>Here, we investigated the role of Shh in the pathologic progress of Parkinson's disease in MPTP-induced animal model system. Interestingly, we observed that Shh expression was gradually increased in MPTP affected SNpc region. Activated microglia exclusively expressed SHH <I>in vivo</I> and we could recapitulate Shh induction in activated cultured primary microglia cells. Using the SHH responsive Cre-loxP binary genetic reporter transgenic mouse system, we also found that most of the cell types except for oligodendrocyte in the SNpc region reacted to the SHH by MPTP injection. Taken together, activated microglia induced Shh expression and most neural cells except oligodendrocyte responded to microglia-derived SHH in MPTP-treated SN. These results suggest that SHH in activated microglia by MPTP-injection might be involved in the innate processes of recovery from neurotoxin induced injury in the PD animal model system.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sonic hedgehog (Shh) was induced by MPTP neurotoxin at the Substantia Nigra (SN) <I>in vivo.</I> </LI> <LI> Activated microglia are major cell type for SHH expression <I>in vivo</I> and <I>in vitro.</I> </LI> <LI> Different types of cells in the brain, except oligodendrocyte, respond to microglia-derived SHH in SN region. </LI> </UL> </P>

Electrochemical Desalination of a 50% w/w Sodium Hydroxide Solution, a Pharmaceutical Sterilization Agent

Jaehong Lee,Ji-hyun Yang,Eugene Huh,Sewon Park,Bonmoo Koo,Ik-Sung Ahn The Korean Electrochemical Society 2023 Journal of electrochemical science and technology Vol.14 No.1

Sodium hydroxide solutions are often employed as sterilization agents in the pharmaceutical industry. Here, the chloride content is considered as a critical impurity. In this study, an electrochemical method was developed to remove chloride ions (Cl^-) through the oxidative deposition of AgCl on a Ag anode. The Cl^- content in the commercially available 50% w/w NaOH solution employed was approximately 100 mg Cl^-/kg NaOH. As the OH^- content is approximately 18,000 times higher than the Cl^- content, the formation of AgCl may be expected to be thermodynamically less favorable than the formation of Ag₂O. However, activation energies for AgCl and Ag₂O formation have been reported to be approximately 3.8 and 31.2 kJ/mol, respectively, and indicate that AgCl formation is favored. AgCl can be selectively produced by controlling the anode potential. Here, the Cl^- concentration was reduced to less than 50 mg Cl^-/kg NaOH when an anode potential of 0.18 or 0.19 V vs. Hg/HgO (reference electrode) was applied for one hour at 50℃. XRD analysis and visual monitoring of the Ag anode confirmed the oxidative deposition of AgCl on the anode surface as well as the electrochemical desalination of the concentrated NaOH solution.

Redox-sensitive colorimetric polyaniline nanoprobes synthesized by a solvent-shift process

Choi, Jihye,Hong, Yoochan,Lee, Eugene,Kim, Myeong-Hoon,Yoon, Dae Sung,Suh, Jinsuck,Huh, Yongmin,Haam, Seungjoo,Yang, Jaemoon Springer-Verlag 2013 Nano research Vol.6 No.5