• Journal of Ginseng Research
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• v.45 no.4
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• pp.465-472
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• 2021

Background: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. Methods: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues. Results: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein. Conclusion: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.531-540
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• 2022

Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca²⁺ concentration ([Ca²⁺]_i) spikes and neuronal cell death induced by 0.1 mM Mg²⁺ and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using imaging methods for Ca²⁺ and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg²⁺ concentration ([Mg²⁺]_o) to 0.1 mM induced repetitive [Ca²⁺]_i spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca²⁺]_i spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca²⁺]_i spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The IP₃ receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca²⁺]_i spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca²⁺ from IP₃ and ryanodine-sensitive intracellular stores and activating TRPC channels.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.672-677
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• 2007

Purpose : To assess the prevalence and characteristics of headache comorbidity with epilepsy in children and adolescents in a specialty epilepsy clinic. Methods : Two hundred twenty nine consecutive patients attending the Chosun University Hospital Pediatric Epilepsy Clinic (mean age $10.0{\pm}4.1\;years$, range 4-17, M:F ratio 1.1:1.0) were interviewed with a standardized headache questionnaire. Headache was classified according to the International Classification of Headache Disorders, 2nd Edition and epilepsy was classified according to the International League Against Epilepsy. Disability was assessed using pediatric migraine disability assessment (PedMIDAS). Results : Of the 229 epilepsy patients, 86 (37.6%) had co-morbid headache. Of the headache patients, 64 (74.4%) had migraine (65.6%- migraine without aura, 20.3% - migraine with aura, 14.1% - probable migraine). The mean headache frequency was $7.2{\pm}8.4$ per month, mean duration was $2.2{\pm}4.0$ hours, mean severity was $5.2{\pm}2.2$ out of 10, and mean PedMIDAS score was $13.0{\pm}35.4$. The proportion of females was not higher in epilepsy with headache patients (48.8%) compared to epilepsy patients alone (48.0%). In the patients with migraine, 48.4% had complex partial seizures, 17.2% had simple partial seizures, and 34.4% had generalized seizures (P=0.368). A postictal association of migraine was reported in 18.8% with 17.2% reporting a preictal headache, and 7.8% reporting an ictal headache. Conclusion : The prevalence of headache in pediatric epilepsy is higher than that in general pediatric population, suggesting a co-morbidity of headache in epilepsy patients with migraine being the most frequent headache disorder. Altered cerebral excitability resulting in an increased occurrence of spreading depression may explain the headache comorbidity with epilepsy. Further studies are needed to assess the etiology of this co-morbidity as well as assess the frequency, duration, severity and disability response to antiepileptic drugs.

• The Korean Journal of Physiology
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• v.20 no.1
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• pp.17-29
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• 1986

The present study was carried out to observe the effect of triiodothyronine on heart, one of the target organ of thyroid hormone. There are many reports that tachycardia, arrythmia, and agumentation of sodium, potassium pump activity are caused in hyperthyroid animal. To examine these cardiac positive chronotropic effects on sinoatrial (SA) node and atrial muscle, hyperthyroid state was induced experimentally by the injecion of 3,3',5-1-triiodothyronine $(T_3)$ in $3{\sim}6$ month-old rabbits. Then intracellular recordings by inserting glass microelectrode into cell were obtained in SA node and atrial muscle. The results can be summarized as follows : 1) Heartbeat was increased from $169.6{\pm}28.0\;to\;264.2{\pm}18.0$ beats per minute, while body weight was decreased to 68f of the initial body weight (Day 1). 2) In experimental group, the duration of action potential at 80% repolarization was decreased from $148.0{\pm}29.1\;to\;107{\pm}13.6msec$. This suggested the increase heartbeat. 3) The firing rate in hyperthyroid group markedly reduced under the 15 mM potassium Tyrode (p<0.005). 4) In hyperthyroid group, depolarization of atrial muscle cell was lowered significantly in 15 mM (p<0.05), 20 mM (p<0.05) potassium Tyrode solution. 5) Sodium-potassium pump activities in experimental group were higher than those in control group in both SA node (p<0. 1) and atrial muscle (p<0.025). 6) In lower concentration of $MnCl_2$, the excitability of SA node in hyperthyroid group was decreased more than that in control group. Effective inhibitory dose $(ID_{50})$ as 0.6 mM in hyperthyroid statd and 1.1 mM in control group.