• 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.

• Biomolecules & Therapeutics
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• 제8권4호
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• pp.325-331
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• 2000

The present study was designed to assess the role of spinal adenosine $A_2$ receptor in the regulation of cardiovascular functions such as mean arterial pressure (MAP) and heart rate (HR) in male Sprague-Dawley rats. Rats (250~300 g) were anesthetized with urethane and paralyzed with d-tubocurarine and artificially ventilated. blood pressure and HR were continuously monitored via a femoral catheter connected to a pressure transducer and a polygraph. Drugs were administered intrathecally using injection cannula through guide cannula which was inserted inthrathecally at lower thoracic level through a puncture of an atlantooccipital mombrane. Intrathecal injection of an adenosine $A_2$ receptor agonist, 5'-(N-cyclopropyl)-carboxamaidoadenosine (CPCA; 1, 2 and 3 nmol, respectively), produced a dose-dependent decrease in MAP and HR. Pretreatment with $N^{G}$-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or 10 nmol of MDL-12,330, an adenylate cyclase inhibitor blocked significantly the depressor and bradycardic effect of 2 nmol of CPCA. But, Pretreatment with 3 nmol of bicuculline, gamma-aminobutyric acid A (GAB $A_{A}$) receptor antagonist, or 50 nmol of 5-aminovaleric acid, GAB $A_{B}$ receptor antagonist did not inhibit the depressor and bradycardic effect of 2 nmol of CPCA. These results indicate that adenosine $A_2$ receptor in the spinal cord plays an inhibitory role in the regulation of cardiovascular function and that the depressor and bradycardic action of adonosine $A_2$ receptor are mediated via the synthesis of nitric oxide and the activation of adenylate cyclase in the spinal cord of rats.s.s.s.

• Journal of Ginseng Research
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• 제34권4호
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• pp.304-313
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• 2010

This study was undertaken to discover the effects and possible mechanisms of the effect of red ginseng extract (RGE) on spontaneous sleep. The effects of a low dose (10 mg/kg) and a high dose (200 mg/kg) of RGE were compared in rats. After recovery from a surgical operation enabling electroencephalograms recordings, rats were administered RGE orally. RGE was administered orally for 1 day or once per day for 5 days in either 10 or 200 mg/kg doses. Polygraphic signs were recorded for 12 h after oral administration of RGE. Both treatment with a large dose (200 mg/kg) of RGE for one day and treatment with either a large or a small dose for 5 days reduced the number of sleep.wake cycles. Daily treatment with RGE (either 10 or 200 mg/kg) for 5 days augmented NREM and total sleep, but reduced wakefulness. Delta wave activity recorded during non-REM (NREM) sleep and REM sleep was increased after one treatment with RGE (either 10 or 200 mg/kg). Delta wave activity during NREM was enhanced after daily treatment with RGE (either 10 or 200 mg/kg) for 5 days. Both alpha and beta subunits of the $\gamma$-aminobutyric acid $(GABA)_A$ receptor were significantly over-expressed in the hypothalamus of the RGE-treated groups. Moreover, the expression of glutamic acid decarboxylase was also increased in the hypothalamus. These results demonstrate that RGE may regulate spontaneous sleep via $GABA_A$ergic systems.

• Journal of Ginseng Research
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• 제36권4호
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• pp.403-410
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• 2012

The current inquiry was conducted to assess the change in sleep architecture after long periods of administration to determine whether ginseng can be used in the therapy of sleeplessness. Following post-surgical recovery, red ginseng extract (RGE, 200 mg/kg) was orally administrated to rats for 9 d. Data were gathered on the 1st, 5th, and 9th day, and an electroencephalogram was recorded 24 h after RGE administration. Polygraphic signs of unobstructed sleep-wake activities were simultaneously recorded with sleep-wake recording electrodes from 11:00 a.m. to 5:00 p.m. for 6 h. Rodents were generally tamed to freely moving polygraphic recording conditions. Although the 1st and 5th day of RGE treatment showed no effect on power densities in nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, the 9th day of RGE administration showed augmented ${\alpha}$-wave (8.0 to 13.0 Hz) power densities in NREM and REM sleep. RGE increased total sleep and NREM sleep. The total percentage of wakefulness was only decreased on the 9th day, and the number of sleep-wake cycles was reduced after the repeated administration of RGE. Thus, the repeated administration of RGE increased NREM sleep in rats. The ${\alpha}$-wave activities in the cortical electroencephalograms were increased in sleep architecture by RGE. Moreover, the levels of both ${\alpha}$- and ${\beta}$-subunits of the ${\gamma}$-aminobutyric acid $(GABA)_A$ receptor were reduced in the hypothalamus of the RGE-treated groups. The level of glutamic acid decarboxylase was over-expressed in the hypothalamus. These results demonstrate that RGE increases NREM sleep via $GABA_A$ergic systems.

• Journal of Ginseng Research
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• 제35권2호
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• pp.219-225
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• 2011

Korean red ginseng (KRG) is a valuable and important traditional medicine in East Asian countries and is currently used extensively for botanical products in the world. KRG has both stimulatory and inhibitory effects on the central nervous system (CNS) suggesting its complicated action mechanisms. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Some studies reported that KRG has antinociceptive effects, but there are few reports of the functional studies of KRG on the SG neurons of the Vc. In this study, a whole cell patch clamp study was performed to examine the action mechanism of a KRG extract on the SG neurons of the Vc from juvenile mice. KRG induced short-lived and repeatable inward currents on all the SG neurons tested in the high chloride pipette solution. The KRG-induced inward currents were concentration dependent and were maintained in the presence of tetrodotoxin, a voltage gated $Na^+$ channel blocker. The KRG-induced inward currents were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and/or picrotoxin, a gamma-aminobutyric acid $(GABA)_A$ receptor antagonist. However, the inward currents were not suppressed by d,l-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. These results show that KRG has excitatory effects on the SG neurons of the Vc via the activation of non-NMDA glutamate receptor as well as an inhibitory effect by activation of the $GABA_A$ receptor, indicating the KRG has both stimulatory and inhibitory effects on the CNS. In addition, KRG may be a potential target for modulating orofacial pain processing.

• The Korean Journal of Pain
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• 제32권3호
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• pp.160-167
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• 2019

Background: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions: It seems that antinocicptive effects of artemisinin are mediated by $GABA_A$ receptors.

• 한방비만학회지
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• 제18권2호
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• pp.83-95
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• 2018

Objectives: The aim of this study was optimized mixing ratio of mulberry leaf, mulberry fruit, and silkworm for amelioration of the metabolic syndrome by using response surface method (RSM). Methods: Antioxidant, antidiabetic and antihypertensive activities of fifteen mixed powder of mulberry leaf, mulberry fruit, and silkworm by RSM were measured as indicators of metabolic syndrome. Results: The optimal mixing ratio of mulberry leaves, mulberry fruits, and silkworm with the greatest antioxidant, antidiabetic and antihypertensive activities was as follows: 2.5890 of mulberry leaf (A), 0.1222 of mulberry fruit (B), 2.9999 of silkworm (C). At this time, it was predicted that the total polyphenol content was estimated to be 185.51 tannic acid equivalent mg/g, 1, 1-diphenyl-2-picrylhy drazyl radical scavenging activity 84.77%, 1-deoxynojirimycin content 415.66 mg/100 g, ${\alpha}-glucosidase$ inhibitory activity 64.31%, ${\gamma}-aminobutyric$ acid content 267.77 mg/100 g, potassium content 1,899.11 mg/100 g, and angiotensin-converting-enzyme inhibitory activity was estimated to be 73.78%. Conclusions: It was concluded that the significant effect of the mulberry leaf, mulberry fruit, and silkworm on the metabolic syndrome-related biological activity indices (antioxidant activity, antidiabetic activity and antihypertensive activity) was as follows: 2.5890 of mulberry leaf (A), 0.1222 of mulberry fruit (B), 2.9999 of silkworm (C).

• 한국식품영양과학회지
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• 제44권4호
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• pp.564-572
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• 2015

본 연구는 백하수오가 가지는 일반 성분과 영양 성분에 대한 탐색을 실시하였다. 무기질에서 높은 칼륨 성분을 보이고 있었으며 라디칼 소거능 역시 우수한 것으로 나타났다. 아미노산에서는 유리 및 구성 아미노산 모두 arginine이 높은 함량을 나타냈으며 생리활성이 우수한 것으로 보고되는 ${\gamma}$-aminobutyric acid(GABA) 역시 높은 함량을 보이고 있다. 지방산 조성을 볼 때 필수지방산으로 알려진 linoleic acid가 가장 주된 지방산으로 나타났으며 ${\omega}$-3 계열인 linolenic acid가 존재하는 것으로 볼 때 우수한 영양적 조성을 가지고 있다고 볼 수 있다. 관능검사를 통해 백하수오차의 경우 녹차에 비해 약간의 쓴맛과 단맛이 부족하다고 측정되었으나 농도 조절이나 부재료 첨가를 통해 개선할 수 있을 것으로 판단된다.

• 한국식품저장유통학회지
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• 제23권3호
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• pp.326-334
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• 2016

오미자 열매를 이용하여 기능성물질인 GABA를 강화시킨 오미자 젖산발효음료를 개발하기 위해서 L. plantarum EJ2014에 의한 젖산발효 최적화를 수행하였다. 오미자 열매 추출액을 젖산 발효시킨 경우 발효 2일 동안 생균수 $4.0{\times}10^7CFU/mL$수준을 유지하면서 젖산균 증식이 미비하였지만 영양성분 YE와 MSG를 함께 첨가한 경우 50배 정도 증가된 $2.2{\times}10^9CFU/mL$생균수를 나타내었다. 특히 젖산발효 3일 동안에 대조군, MSG, YE를 각각 첨가군에서 초기 pH 3-4 수준에서 유지되었다. 반면에 YE와 MSG를 함께 첨가한 발효물은 pH가 증가되면서 pH 5.0 이상을 나타내었으며, 초기 산도 1.74%에서 발효 3일에 0.56% 수준으로 감소하였다. 오미자 열매 추출물인 대조군과 2% MSG 또는 0.5% YE만을 첨가한 조건에서는 GABA로 소량 전환되는 것으로 나타났다. 반면에 MSG와 YE를 함께 첨가한 경우 젖산발효 1일째부터 GABA가 생성되면서 3일째에는 MSG 2%를 거의 소진하는 것으로 나타났으며, HPLC 정량분석으로 0.92% GABA 생성이 확인되었다. MSG와 YE함께 첨가한 발효조건에서는 젖산발효 1일째부터 발효물은 붉은 색이 퇴색되면서 황색으로 변화하였으며, 발효 초기에 적색을 나타내는 a값이 15.74에서 발효 후에 5.39로 크게 감소하는 것으로 나타났다. 색, 맛, 향 등을 포함한 전반적인 기호도를 나타낸 관능평가에서 오미자 착즙 원액과 발효물 100%인 실험군에서 점수가 각각 4.50, 4.33을 기록하여 상대적으로 낮은 기호도를 나타낸 반면에 발효물 50% 첨가한 실험군이 6.33으로 가장 높은 기호도 점수를 나타내었다. 오미자 열매 추출액에 오미자 발효물을 50% 첨가함으로서 기호성이 우수하며 고농도 GABA와 probiotic을 함유한 오미자 발효음료의 제조가 가능하였다.

• 한국식품영양과학회지
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• 제44권9호
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• pp.1295-1303
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• 2015

국내에서 주로 재배되는 대표적인 베리류에 대한 화학 조성 및 기능성을 알아보고자 일정 시기에 수확한 오디, 블랙라즈 베리, 라즈베리, 블루베리의 pH, 산도, 유리당, ${\gamma}-aminobutyric$acid(GABA), 무기질 함량, phenolic compound, 항산 화 활성을 조사하여 비교하였다. 베리류 4종의 pH는 3.3~5.2로 블루베리가 가장 낮았고 오디가 가장 높은 반면, 산도는 0.26~1.10%(w/w)로 오디가 가장 낮았고 블랙라즈 베리가 가장 높았다. 베리류에서 검출된 유리당인 fructose와 glucose는 같은 비율로 존재하였고, 그 총량은 4.80~12.93%(w/w)로 오디가 가장 높았으며 블랙라즈베리가 가장 낮았다. GABA는 오디에 69.3 mg/100 g이 함유되어 있었는데, 이는 다른 베리류에 비해 3배 이상 많은 양이다. 베리류에 함유된 주요 무기질은 칼륨, 칼슘, 마그네슘이었고, 총 무기질 함량은 92.9~256.0 mg/100 g으로 블랙라즈 베리에 유의적으로 높게 함유되어 있었으며(P<0.05) 블루베리가 가장 낮았다. Total polyphenol과 total flavonoid 함량은 각각 198.2~547.2 mg/100 g과 5.0~94.6 g/100 g의 범위로 블랙라즈베리가 가장 높았고, 라즈베리는 유의적으로 가장 낮았다(P<0.05). Total anthocyanin은 19.8~385.6 mg/100 g의 범위로 블랙라즈베리가 가장 높았고, 라즈베리가 유의적으로 낮았다(P<0.05). Total PA(phenolic acids)는 블랙라즈베리와 라즈베리에 각각 14.0 mg/kg과 5.9 mg/kg이 함유되어 있었는데 이는 오디에 함유된 50.4 mg/kg보다 낮았으며, 391.4 mg/kg으로 가장 높게 함유된 블루베리에는 PA의 대부분이 chlorogenic acid였다. 베리류 4종의 항산화 활성을 DPPH 및 ABTS free radical scavenging activity를 분석하여 Trolox equivalent 값으로 나타낸 결과 Trolox equivalent antioxidant capacity와 total polyphenol, total anthocyanin, total flavonoid 함량 과는 유의적인 양(+)의 상관관계(Pearson 상관계수 r${\geq}0.85$; P<0.01)를 나타내었고, 블랙라즈베리가 DPPH 및 ABTS 항산화 활성이 가장 우수하였다.