• Biomolecules & Therapeutics
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• 제15권3호
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• pp.175-181
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• 2007

Zizyphi Spinosi Semen (ZSS), a traditional Chinese folk medicine, has been used for treatment of insomnia and anxiety. This experiment was performed to investigate the anxiolytic-like effect of methanol extract of ZSS (MEZSS) in mice by using the experimental paradigms of anxiety and compared with that of a known anxiolytic, diazepam. In the elevated plus-maze test, it showed that MEZSS (100 mg/kg, p.o.) and diazepam (2.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries. MEZSS (50, 100 and 200 mg/kg, p.o.) and diazepam (0.5 mg/kg, p.o.) significantly increased the number of head dips compared with that of control group in the hole-board test. However, MEZSS has no effect on decreasing the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly inhibited locomotor activity. MEZSS did not decrease the strength force in the grip strength test, either. In addition, GABAergic involvements were also investigated to understand the possible mechanisms. $GABA_{A}$ receptors subunits and glutamic acid decarboxylase (GAD) were not over expressed, compared with that of the saline group. We also found that MEZSS did not increase chloride influx in cultured cerebellar granule cells. It is concluded that MEZSS might have anxiolytic-like effects, but these effects might not be mediated by GABAergic transmission.

• 대한유전성대사질환학회지
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• 제14권2호
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• pp.191-194
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• 2014

사립체 근병증은 사립체 호흡 사슬의 장애로 인한 것으로 내분비계 관련 증상이 흔히 동반되고 그 중 당뇨병이 상대적으로 높은 빈도를 보인다고 알려져 있다. 사립체 근병증에서의 당뇨병은 사립체 기능 장애로 인한 인슐린 분비의 결함으로 발생하고, 대개 인슐린 의존성이나 당뇨병성 케톤산증으로 발현하거나 자가 항체가 검출되는 경우는 드물다. 저자들은 사립체 근병증 환자에서 당뇨병성 케톤산증으로 발현하고 Anti-GAD antibody와 Anti-insulin auto-antibody가 모두 양성으로 확인된 인슐린 의존성 당뇨병을 진단하였기에 이를 기존의 문헌과 비교하여 보고하는 바이다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.27-36
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• 2017

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of $GABA_A$-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and $0.1{\mu}g/ml$) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of $GABA_A$-ergic systems, and can be useful in the treatment of insomnia.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.586-592
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• 2017

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via ${\gamma}$-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN 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.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through $GABA_A$-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• 한국발생생물학회지:발생과생식
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• 제14권1호
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• pp.35-41
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• 2010

Mammalian reproduction is regulated by a feedback circuit of the key reproductive hormones such as GnRH, gonadotropin and sex steroids on the hypothalamic-pituitary-gonadal axis. In particular, the onset of female puberty is triggered by gain of a pulsatile pattern and increment of GnRH secretion from hypothalamus. Previous studies including our own clearly demonstrated that genistein (GS), a phytoestrogenic isoflavone, altered the timing of puberty onset in female rats. However, the brain-specific actions of GS in female rats has not been explored yet. The present study was performed to examine the changes in the activities of GnRH neurons and their neural circuits by GS in female rats. Concerning the drug delivery route, intracerebroventricular (ICV) injection technique was employed to eliminate the unwanted actions on the extrabrain tissues which can be occurred if the testing drug is systemically administered. Adult female rats (PND 100, 210-230 g BW) were anaesthetized, treated with single dose of GS ($3.4{\mu}g$/animal), and sacrificed at 3 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly raised the transcriptional activities of enhanced at puberty1 (EAP-1, p<0.05), glutamic acid decarboxylase (GAD67, p<0.01) which are known to modulate GnRH secretion in the hypothalamus. However, GS infusion could not change the mRNA level of nitric oxide synthase 2 (NOS-2). GS administration significantly increased the mRNA levels of KiSS-1 (p<0.001), GPR54 (p<0.001), and GnRH (p<0.01) in the hypothalami, but decreased the mRNA levels of LH-$\beta$ (p<0.01) and FSH-$\beta$ (p<0.05) in the pituitaries. Taken together, the present study indicated that the acute exposure to GS could directly activate the hypothalamic GnRH modulating system, suggesting the GS's disrupting effects such as the early onset of puberty in immature female rats might be derived from premature activation of key reproduction related genes in hypothalamus-pituitary neuroendocrine circuit.

• 생명과학회지
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• 제17권7호통권87호
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• pp.970-975
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• 2007

국내해안의 젓갈과 김치류로부터 86종의 GABA 생산균주를 분리하였다. 분리된 균주들을 Thin layer chromatography를 이용하여 GABA 생성능이 우수한 AML15, AML45-1, AML72의 3종의 균주를 선발하였다. 선별된 3종의 균주의 아미노산 분석 결과 GABA 생성능이 가장 우수한 AML15 균주를 본 실험에 사용하였다. AML15의 분류학적 위치를 규명하기 위하여 16S ribosomal DNA 영역의 부분염기서열 분석을 실시하였다. 165 rDNA 분석결과 Lactobacillus brevis ATCC 367과 99%의 유사도를 나타내어 L. brevis AML15로 명명하였다. MRS 배지에 최종 전환 농도로 설정된 5%(w/v) monosodium glutamic acid를 첨가하고 배지의 초기 pH를 4.0, 5.0과 6.0으로 조정하여 배양한 결과 배지의 초기 pH가 5.0일 때 GABA 생성능이 가장 높게 조사되었다. GABA 생산배지에 GAD 효소활성에 조효소로 작용하는 PLP를 0. 10. 50과 100 ${\mu}M$의 농도로 첨가하여 아미노산 분석결과 PLP를 10${\mu}M$ 첨가하였을 때 10,424 $nM/{\mu}$l의 GABA가생산되었다. PLP를 첨가하지 않았을 때보다 PLP 첨가 후 GABA 생성이 증가됨을 확인할 수 있었다.

• 동아시아식생활학회지
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• 제17권2호
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• pp.205-212
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• 2007

This study was designed to investigate a natural medicinal multi-plants extract (BG515), which consisted of multi extracts of Mori folium, Rehmannia glutinosa Liboschitz, Dioscorea japonica, Lycii fructus, and Astragalus radix, on blood glucose, insulin levels, and serum malondialdehyde (MDA) concentrations in streptozotocin-induced diabetic rats. Streptozotocin (STZ) induces a type 1 diabetes mellitus in rats. Type 1 is usually characterized by the presence of islet cell autoantibodies (ICA), autoantibodies to insulin (IAA), and autoantiboides to glutamic acid decarboxylase (GAD), which identify the autoimmune process that leads to $\beta-cell$ destruction. Thirty-five male Sprague-Dawley (SD) rats weighing $150\sim170g$ each (6 weeks old) were randomly divided into one control (Group A) and 4 STZ-induced diabetic groups, and were subjected to one of the following treatment for 12 weeks. Groups A and B were fed basal diets and Group C, D, and E received the same diets as groups A and B, but with supplements of 150 mg/kg, 300 mg/kg, and 600 mg/kg of BG515 orally for 12 weeks, respectively. Diabetes was induced in Groups B, C, D, and E by intravenous injection of 45 mg/kg of STZ per body weight in sodium citrate buffer (pH 4.5) via the tail vein. In the BG515 groups, we found increases in serum insulin levels, compared to the STZ-control group, but these data were not significant. In contrast, blood glucose and serum MDA concentrations decreased in the BG515 groups compare to the STZ-control group. At the 5th week, in all the BG515 administered groups, there were decreases in serum blood glucose levels compared to the STZ- control group, and this activity was very strong in the BG515-1 group at the 12th week. These results suggest that natural bio-complex compounds (BG515) may slightly suppress STZ-induced changes in serum MDA concentration via the maintenance of serum insulin levels, due to the prevention of $\beta-cell$ and glucagon destruction by STZ.