• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.328-335
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• 2008

This study was undertaken to investigate whether honokiol could enhance the pentobarbitalinduced sleeping behaviors through $\gamma$-aminobutyric acid (GABA) receptor $Cl^-$ channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and $Cl^-$ sensitive fluorescence probe were used to detect the expression of $GABA_A$ receptor subunits and $Cl^-$ influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 ${\mu}M$) increased $Cl^-$ influx in primary cultured cerebellar granule cells, and selectively increased the $GABA_A$ receptor $\alpha$-subunit expression, but had no effect on the abundance of $\beta$ or $\gamma$-subunits. Chronic treatment with 20 ${\mu}M$ honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through $GABA_A$ receptor $Cl^-$ channel activation.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.55-65
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• 2010

목적 : 기존 연구에서 신문혈 자침은 알코올 및 코카인을 자가섭취하는 동물 모델에서 효과적이라는 점이 밝혀졌으며, 또한 모르핀 자가섭취를 억제할 수 있음이 밝혀졌다. 이러한 결과를 바탕으로 본 연구에서는 자침의 효과가 얼마나 지속될 수 있는지 알아보았다. 재료 및 방법 : 체중 270~300g의 수컷 SD계 흰쥐를 이용하였다. 먹이섭취 훈련을 통과한 후 오른쪽 경정맥에 관을 삽입하는 수술을 거쳐, 0.1mg/kg의 모르핀을 매일 1시간, 총 3주 동안 자가섭취 하도록 하였다. 모르핀을 일정하게 섭취한 동물에게는 다음날 침술을 시행하였다. 두 번째 실험에서는 GABAA 및 GABAB 길항제를 자침 30분 전에 투여하여 침술의 효능과 GABA 수용체계 사이의 관계를 검증하였다. 결과 : 모르핀 자가섭취를 억제하는 신문혈 자침의 효과는 매일 비슷하게 나타나지 않았으며, 4일째에는 유의한 효과가 없는 것으로 나타났다. 그러나 5일째와 6일째에는 다시 유의한 효과가 나타나 뒤집어진 U 자형 곡선을 나타내었다. 또한 GABA 수용체의 길항제들은 자침의 효과가 유의하게 나타났을 때 이를 차단하는 결과를 보였다. 결론 : 모르핀 중독 치료에서 침술의 효과는 항상 비슷하게 발휘되는 것이 아니므로 침 치료는 적어도 1주일에 2회 이상 받을 필요가 있다. 아울러 보다 심도 있는 연구를 위하여 뇌신경 체계에 대한 연구가 이루어질 필요가 있는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.59-69
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• 2010

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists ($1{\mu}g$ bicuculline/rat and $5{\mu}g$ phaclofen/rat), agonists ($1{\mu}g$ muscimol/rat and $0.5{\mu}g$ baclofen/rat) or GABA transporter (GAT) inhibitors ($20{\mu}g$ NNC-711/rat and $1{\mu}g$ SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.

• Journal of Korean Ophthalmic Optics Society
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• v.20 no.3
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• pp.391-396
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• 2015

Purpose: The objective of this study was to investigate the visual system of the greater horseshoe bat (Rhinolophus ferrumequinum) by location analysis of some major neurotransmitters glutamate, ${\gamma}$-aminobutyric acid (GABA), acetylcholine, and their receptors, and $m{\ddot{u}}ller$ glial cells in retina. Methods: Standard immunocytochemical techniques were used after vibratome section of retinal tissues of adult greater horseshoe bat for this study. Immnoreactions in immunofluorescence images were analyzed using confocal microscope. Results: Anti-glutamate-immunoreactive neurons were mainly localized in the ganglion cell layer (GCL). The majority of anti-GABA-immunoreactive cells distributed in the inner nuclear layer (INL), and GABAA receptors were localized in the inner plexiform layer (IPL). Anti-choline acetyltransferase-immuoreactive cholinergic neurons were mainly located in the INL and GCL, and most of nicotinic acetylcholine receptors were localized in the IPL. The $m{\ddot{u}}ller$ cells in the retina of the greater horseshoe bat stretched theirs range from the GCL to outer nuclear layer (ONL). Conclusions: This study revealed that the retinas of the greater horseshoe bats contain the same major neurotransmitters and receptors, and glial cell in visually functional mammalian retinas. The present results may suggest that the greater horseshoe bats have the functional retinas for visual analysis through the organized retinal neural circuits.

• Food Science and Preservation
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• v.19 no.5
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• pp.767-773
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• 2012

The purpose of this study was to investigate the anxiolytic-like effect of the methanol extract of Sophorae fructus (MESF) using elevated plus-maze (EPM), open field test, and horizontal wire test in mice. MESF was orally administered at doses of 50, 100, 200, or 400 mg/kg to ICR mice 1 h before behavioral evaluation. The control group was given an equal volume of 10% Tween 80, and the positive control group was given diazepam (1 mg/kg, i.p.). The administration of MESF significantly increased the percentage of time spent in open arms and the entries into the open arms of the EPM compared with the 10% Tween 80-treated control group (p < 0.05). In addition, the anxiolytic-like activities of MESF were antagonized by flumazenil (a GABAA antagonist, 10 mg/kg) but not by WAY-100635 (a 5-HT1A antagonist, 0.3 mg/kg). Futhermore, there were no changes in the locomotor activity and myorelaxant effects of the experimental group, as opposed to the 10% Tween 80-treated control group. Therefore, these findings suggest that MESF promotes the anxiolytic-like activity mediated by the GABAergic nervous system in mice.

• The Korean Journal of Zoology
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• v.39 no.1
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• pp.1-11
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• 1996

The SR 95531, a GABA antagonist was microinjected into either the pretectum nuclei (nucleus Superficialis Synencephali nSS) or the nBOR (nucleus Ectomammilaris nEM) of chickens. Monocular optokinetic nystagmus (01(N) was reorded by the search coil technique before and after unilateral intracerebral drug administration. Unilateral microinjections of SR 95531 into either the nSS or nEM induce a reversible increase of gain in OKN directed by contralateral eye for both directions of stimulation. The administration into the nSS increased directional asymmetry by increasing the T~ component velocity gain more strongly than the N-T component velocity gain. On the other hand, the unilateral administration of the drug into the nEM suppressed the diretional O1(N asymmetry by increasing the N-T component velocity gain more strongly than the T-N component velocity gain. The nSS seems especially involved in monocular OKN in response to a T-N stimulation, while the nEM seems more involved in the OKN response to N-T stimulation. These results indicate that the drug suppresses GABAergic inhibition at the mesencephalic level. The increase in gain of OKN directed by the ipsilateral eye to microinjeded nuclei could account for the strong interactions existing between these two mesencephalic structures responsible for horizontal OKN.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.86-95
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• 2020

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 10⁹ CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA_A receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.