• Natural Product Sciences
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• v.22 no.4
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• pp.263-269
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• 2016

Rhynchophylline (RP) is a major tetracyclic oxindole alkaloid of Uncariae Ramulus et Uncus which has been used to treat hypertension, seizures, pain and anxiety in the oriental countries. A recent report revealed that RP attenuated ischemia-induced neuronal damage and kainite-induced convulsions in animals. This study was performed to investigate whether RP enhances pentobarbital-induced sleep behaviors and modulates sleep architecture in mice. Locomotor activity was significantly inhibited by RP at 0.25 and 0.5 mg/kg, similar to 2 mg/kg diazepam (a benzodiazepine agonist) in mice. RP shortened sleep latency and increased total sleep time in a dose-dependent manner when administrated with pentobarbital (42 mg/kg, i.p.). RP also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). On the other hand, RP (0.25 mg/kg, p.o.) itself significantly inhibited sleep-wake cycles, prolonged total sleep time, and rapid eye movement in rats. In addition, RP also increased chloride influx in the primary cultured hypothalamic neuronal cells. In addition, we found that glutamic acid decarboxylase ($GAD_{65/67}$) was activated by RP. In conclusion, RP augments pentobarbital-induced sleeping behaviors, and can be a candidate for treating insomnia.

• BMB Reports
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• v.46 no.2
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• pp.80-85
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• 2013

We investigated the temporal alterations of adrenocorticotropic hormone (ACTH) immunoreactivity in the hippocampus after seizure onset. Expression of ACTH was observed within inter-neurons in the pre-seizure group of seizure sensitive gerbils, whereas its immunoreactivities were rarely detected in seizure resistant gerbil. Three hr after the seizure, ACTH immunoreac-tivity was significantly increased in interneurons within all hippocampal regions. On the basis of their localization and morphology through immunofluorescence staining, these cells were identified as $GABA_A$ ${\alpha}1$-containing interneurons. At the 12 hr postictal period, ACTH expression in these regions was down-regulated, in a similar manner to the pre-seizure group of gerbils. These findings support the increase in ACTH synthesis that contributes to a reduction of corticotrophin-releasing factor via the negative feedback system which in turn provides an opportunity to enhance the excitability of GABAergic interneurons. Therefore, ACTH may play an important role in the reduction of excitotoxicity in all hippocampal regions.

• Natural Product Sciences
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• v.26 no.1
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• pp.1-9
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• 2020

Flavonoids are mainly contained in the vegetables and medicinal herbs. Until now, over 5,000 kinds of flavonoid have been identified and their biological activities have been reported. Among them, we are interested in oroxylin A and spinosin because of their specific structures having bulky group at C-6 of ring A. Oroxylin A is contained in the Scutellaria baicalensis and exhibits cognitive enhancing activity as a GABA_A receptor antagonist, which is different from those of mainly contained in the S. baicalenis, baicalein or wogonin. Spinosin is isolated from Zizyphus jujuba var. spinosa and mainly studied as a hypnotic or anxiolytic agent because of traditional knowledge about its original herb. As far as we know, the cognitive function of spinosin was first identified by our group. In this review, we discuss how such flavonoids exert their pharmacological activities associated with cognitive function based on the receptor binding study and behavioral studies. Traditional knowledge and reverse pharmacology may be addressed in the research field of phytochemical pharmacology and useful to unveil the secret of phytochemicals.

• Animal cells and systems
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• v.1 no.4
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• pp.583-587
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• 1997

Incubation of an NADPH-dependent succinic semialdehyde reductase from bovine brain with N-bromosuccinimide (NBS) resulted in a time-dependent loss of enzyme activity. The inactivation followed pseudo-first-order kinetics with the second-order rate constant of $6.8\times{10}^3$ $M^-1$ $min^{-1}$. The inactivation was prevented by preincubation of the enzyme with substrate succinic semialdehyde, but not with coenzyme NADPH. There was a linear relation-ship between oxindole formation and the loss of enzyme activity. Spectro-photometric studies indicated that about one oxindole group per molecule of the enzyme was formed following complete loss of enzymatic activity. It is suggested that the catalytic function of succinic semialdehyde reductase is modulated by binding of NBS to a specific tryptophan residue at or near the substrate binding site of the enzyme.

• Advances in Traditional Medicine
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• v.9 no.2
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• pp.135-141
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• 2009

The purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a $GABA_A$ antagonist not by WAY 100635 (0.3 mg/kg, i.p), a 5-$HT_{1A}$ receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

• Food Science and Biotechnology
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• v.18 no.3
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• pp.799-802
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• 2009

The effect of germination on hydration and germination properties, and on the changes of fatty acids and amino acids profiles of a brown rice 'Keunnun' (KN) with a large embryo was compared to 'Ilpumbyeo' (IP) with a normal embryo. A rapid germination up to 24 hr was observed in both brown rice cultivars, afterward decreased with germination time. At 60 hr, the KN ($86.0{\pm}4.24%$) showed slightly lower germination capability than the IP ($97.0{\pm}1.41%$). Lower water uptake during germination was also found in the KN ($1.22{\pm}0.02\;g$) compared to the IP ($1.59{\pm}0.05\;g$). Major fatty acids were palmitic acid, oleic acid, and linoleic acid accounting for more than 95% of total fatty acids. The most abundant amino acid in both types was oleic acid, which was decreased during germination, whereas palmitic and linoleic acids were increased. Eight amino acids were detected, and a remarkable increase in ${\gamma}-amino$ butyric acid (GABA) during germination was observed. The KN was characterized with higher tasty amino acids of aspartic acid, glutamic acid, glycine, and alanine.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.97-104
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• 1996

Different neural substrates have been reported to be implicated in analgesic mechanisms in the acute phasic and the sustained tonic pains. To explore the differential antinociceptive action of diphenylhydantoin (DPH) and carbamazepine (CBZ) on the acute phasic and the tonic pains, changes in tail flick latency, hot plate latency and the formalin-induced nociceptive score were assessed prior to and after intraperitoneal administration of DPH (20 & 40 mg/Kg) and CBZ (20 mg/Kg). In 11 rats, CBZ was administered repeatedly for 6 days at the dose of 20 mg/Kg/day. Also studied were the effects of strychnine and picrotoxin (1 mg/Kg, i.p.) on the CBZ-produced changes in the formalin-induced pain behaviors. The tail flick and hot plate ltencies were not changes after administration of DPH and CBZ. However DPH strongly suppressed the formalin-induced tonic pain. A single and the repeated administration of CBZ inhibited both the early phasic and the late tonic pain responses to formalin in n similar manner. On the other hand, the antinociceptive actions of CBZ were not altered by strychnine or picrotoxin. These experimental findings lead to the conclusion that DPH and CBZ have differential antinociceptive action on the acute and the tonic pains and that their antinociceptive actions are independent of the GABA- and glycine-receptors.

• Korean Journal of Pharmacognosy
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• v.44 no.3
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• pp.281-285
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• 2013

Ethanol extract of Gastrodia elata fermented with Lactobacillus brevis was highly effective on the duration of pentobarbital hypnosis in mice. Pretreatment of mice with ethanol extract of the fermented Gastrodia elata (200 mg/kg, p.o.) prolonged markedly the duration of pentobarbital sleeping time and reduced the sleep latency. The mechanism of the extract of the fermented Gastrodia elata was investigated to inhibit the binding of $^3H$-Flumazenil, a selective benzodiazepine receptor antagonist, to benzodiazepine receptor of mice cortices. $IC_{50}$ value from displacement of $^3H$-Flumazenil binding was 62 ${\mu}g/mL$ at the treatment of the fermented Gastrodia elata. Therefore, these finding, such as increase of sleeping time and reduction of sleep latency, was examined by elevated concentration of GABA and parishin C, which were increased by Lactobacillus brevis.

• Food Science and Biotechnology
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• v.15 no.3
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• pp.351-356
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• 2006

In this study, we investigated the effect of adding a 1, 3, or 5% solution of germinated brown rice concentrate (GBRC) to fermented kimchi. During fermentation, the concentration of free amino acids and essential amino acids increased with increasing concentrations of GBRC. In particular, higher levels of free amino acids were associated with a sweet taste compared with controls. The ${\gamma}$-aminobutyric acid (GABA) content of kimchi containing the 5% GBRC solution was 3 times higher than that of controls. The total phenolic compound content (130 mg%) did not change significantly in the control group, but increased in 10 mg% increments as the GBRC concentration rose from 1 to 3 to 5%. 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging activity and superoxide radical scavenging activity also increased with the GBRC concentration, with maximum activity during the ripe stage with GBRC measured at 79 to 82% compared with controls (30 to 71 %). The nitrite scavenging activity was 10% higher with GBRC compared with controls and was highest when the pH was 1.2. These results showed that the addition of GBRC is effective in improving the function of kimchi.

• Food Science and Industry
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• v.50 no.3
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• pp.93-104
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• 2017

monosodium L-glutamate (MSG), composed of 88% L-glutamic acid (GLU) and 12% Na, is considered as Generally Recognized as Safe. GLU is accounting for 15% of the total amino acid content in our body. Daily GLU intake is large 3.5-10.6 g from food and 1.3 g from food additive. The daily formed GLU in the body, via degradation of the total protein, is 48-50 g (70 kg of male) and the maintained GLU in the body is total bound GLU (1.4-2.0 kg) and free GLU (10 g). About 88% GLU are consumed at digestive tract, and only 12% GLU enter the blood stream. GLU is generally known to precursors of N-acetyl glutamate and glutamine, substrates for protein synthesis, a neurotransmitter (GABA), and the active site of the enzyme. In addition to protein synthesis, GLU has these key functions within the body, thus this amino acid is critical for healthy body maintenance and function.