• 대한본초학회지
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• 제24권1호
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• pp.179-189
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• 2009

Objectives : Coptidis Rhizoma (Coptis japonica MAKINO; CR) is a well known crude drug as antimicrobial, antibacterial, anti-inflammatory, antioxidant activity. However, there is no study of the effect of CR on brain infarction and it's mechanism. The aim of this study was to investigate the effects on ischemic stroke induced by photothrombotic infarction by evaluating the functional & neuronal recovery after brain infarction. Materials & Methods : Male Sprague-Dawley rats (250-300 g) were induced photothrombotic brain infarction on sensorimotor cortex, and brain infarction volume by image J software (NIH, USA) after Nissl stain, also single pellet reaching task as a functional motor recovery were observed. After orally pretreated by CR (500 mg/kg) or normal saline as a sham control before 7 days from the time of photothrombotic infarction, rats were sacrificed. After then we analysed anti-inflammatory cytokines (TNF-$\alpha$, IL-6, IL-1$\beta$), by RT-PCR and ELISA method, and immunohistochemistry (GFAP, connexin-43) as a marker of neural plasticity. Results : CR (100, 250, 500 mg/kg) decreased the infarction volume dose-dependently, however the effect of 500mg/kg of CR (CR 500) showed the best (P=0.051). Also, CR 500 decreased the infarction volume time-dependently, the most effective time was 3-7 days after stroke. Photothrombosis increased inflammatory cytokines after infarction, CR 500 suppressed significantly mRNA expression of IL-1$\beta$, IL-6 and TNF-$\alpha$. In serum, CR 500 decreased the amount of IL-1$\beta$, 12h, 24h and 48h respectively (p < 0.05), also decreased that of IL-6 and TNF-$\alpha$, 12h respectively (p < 0.05) after infarction. The more astrocytes were observed and neural plasticity was facilitated in the rat brain of CR 500 than that of sham control in immunohistochemistry. Conclusions : This results suggest that CR decrease infarction volume and improve functional motor recovery in acute stage in photothrombotic ischemic infarction model in the mechanism of anti-inflammation and promoting neural plasticity.

• Neonatal Medicine
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• 제17권2호
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• pp.181-192
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• 2010

목적: 비경쟁적 NMDA 길항제인 dizocilpine (MK-801)는 저산소성 허혈성 뇌병증, 외상성 뇌손상, 흥분독성과 같은 신경 질환의 동물 모델에서 보호 효과가 있다고 발표되고 있지만 주산기 가사로 인한 저산소성 허혈성 뇌병증의 치료제로서 그 기전이 명확하게 밝혀지지 않았다. 저자들은 dizocilpine을 이용하여 주산기 저산소성 허혈성 뇌병증의 치료제로서 항 세포사멸사을 통한 기전을 알아보고자 하였다. 방법: 생체외 실험으로 재태기간 19일된 태아 흰쥐의 대뇌피질 세포를 배양하여 3군(정상산소군, 저산소군, 뇌손상 전dizocilpine 투여군)으로 나누었다. 정상산소군은 5% $CO_2$ 배양기(95% air, 5% $CO_2$)에 두었고, 저산소군과 뇌손상 전 dizocilpine 투여군($10{\mu}g/mL$)은 1% $O_2$ 배양기(94% $N_2$, 5% CO2)에서 16시간 동안 뇌세포손상을 유도하였다. 생체내 실험으로 저산소성 허혈성 뇌병증의 동물 모델에서는 생후 7일된 신생백서의 좌측 총 경동맥을 결찰한 후 6개 군(정상산소군, 수술 없이 저산소군, sham 수술 후 저산소군, 수술 후 저산소군, vehicle 투여후 저산소군, dizocilpine 투여 후 저산소군)으로 나누었고, 저산소 손상은 특별히 제작한 통속에서 2시간 동안 8% $O_2$에 노출시켰다. Dizocilpine은 뇌손상 전후 30분에 체중 kg당 10 mg를 투여하였고, 저산소 손상 후 7일째 조직을 실험하였다. 생체외 내 실험 모두 세포사멸사와 관련된 Bcl-2, Bax, caspase-3항체와 primer를 이용하여 western blots과 실시간 중합효소연쇄반응을 실시하였다. 결과: 세포사멸사와 관련된 생체외 내 실험에서 Bcl-2의 발현은 저산소군에서 정상산소군보다 감소하였으나 dizocilpine 투여군에서 저산소군보다 증가하였다. 그러나 Bax와 caspase-3 발현 및 Bax/Bcl-2의 비는 반대로 표현되었다. 결론: 본 연구에서 dizocilpine은 항 세포사멸사를 통하여 주산기 저산소성 허혈성 뇌손상에서 신경보호 역할을 하는 것을 알 수 있었다.

• 한국발생생물학회지:발생과생식
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• 제12권2호
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• pp.117-124
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• 2008

지구상의 모든 생명체들은 자신의 생존과 종의 영속성을 보장하기 위해 우호적이지 않은 환경 변화에 대응하기 위한 효과적인 전략을 발전시켜왔다. 그 결과, 생명체들은 환경요인들의 변화에도 불구하고 체내 생리적 환경의 역동적인 평형, 즉 항상성(homeostasis)을 유지해 나간다. 스트레스는 항상성을 위협하는 정서적 그리고 물리적 반응이다. 스트레스는 일시적일 뿐만 아니라 거의 영구적인 영향을 개체에 줄 수 있는데, 특히 출생전 스트레스는 유전 코드의 변경없이 성체의 기능과 구조를 바꿀 수 있는 '후생학적 프로그래밍'을 할 수 있음이 최근의 연구들에 의해 알려졌다. 본 논문에서는 출생 전 스트레스를 받은 수컷 흰쥐에서 나타나는 생식과 연관된 일련의 사건들, 예를 들어 성적 이형현상을 보이는 뇌 지역의 변화, 신경전달물질 대사의 수정, 생식내분비 상태의 변화, 그리고 마지막으로 성행동의 이상들을 소개한다. 태아의 뇌는 출생전 프로그래밍에 극히 민감한데, 특히 글루코코티코이드는 강력한 뇌-프로그래밍 능력을 갖고 있다. 모체 스트레스에 의해 유도된 글루코코티코이드 입력에 의한 태아 뇌의 지속적인 과도 활성은 신경 가소성을 증가시키는 새로운 프로그램을 제공할 것이다. 그리고 증가한 신경 가소성은 환경 도전 속에서 개체가 더 잘 적응하도록 하는 증가된 표현형의 가소성에 대한 기초가 될 것이다. 결론적으로, '혹독한' 환경을 태아기에 경험한 개체는 미래에 자신의 생존 가능성을 높이기 위해 번식능력을 일부 포기하도록 후생학적으로 (재)프로그램하는 것으로 추정된다.

• Journal of Microbiology and Biotechnology
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• 제28권11호
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• pp.1883-1895
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• 2018

Alcohol dependence is a global public health problem, yet the mechanisms of alcohol dependence are incompletely understood. The traditional view has been that ethanol alters various neurotransmitters and their receptors in the brain and causes the addiction. However, an increasing amount of experimental evidence suggests that gut microbiota also influence brain functions via gut-to-brain interactions, and may therefore induce the development of alcohol use disorders. In this study, a rat model of alcohol dependence and withdrawal was employed, the gut microbiota composition was analyzed by high-throughput 16S rRNA gene sequencing, and the metagenome function was predicted by PICRUSt software. The results suggested that chronic alcohol consumption did not significantly alter the diversity and richness of gut microbiota in the jejunum and colon, but rather markedly changed the microbiota composition structure in the colon. The phyla Bacteroidetes and eight genera including Bacteroidales S24-7, Ruminococcaceae, Parabacteroides, Butyricimonas, et al were drastically increased, however the genus Lactobacillus and gauvreauii in the colon were significantly decreased in the alcohol dependence group compared with the withdrawal and control groups. The microbial functional prediction analysis revealed that the proportions of amino acid metabolism, polyketide sugar unit biosynthesis and peroxisome were significantly increased in the AD group. This study demonstrated that chronic alcohol consumption has a dramatic effect on the microbiota composition structure in the colon but few effects on the jejunum. Inducement of colonic microbiota dysbiosis due to alcohol abuse seems to be a factor of alcohol dependence, which suggests that modulating colonic microbiota composition might be a potentially new target for treating alcohol addiction.

• 생명과학회지
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• 제19권3호
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• pp.322-326
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• 2009

간 질환 개선용 영양보충제로 시판되고 있는 글루타티온 고함유 Saccharomyces cerevisiae FF-8 효모 균체(FF-8) 급여가 사염화탄소 및 알코올-유발 흰쥐 조직 스트레스에 대하여 억제효과가 있다는 것을보고한 바 있다. 본 실험에서는 글루타티온 고함유 효모 FF-8 급여에 의한 오르트산-유발 지방간에서 각 조직 중 과산화지질 농도와 간 조직 내 미네랄 성분과의 관계를 검토하였다. 체중 증가량은 정상군은 두 실험군에 비해 증가하였으나, 오르트산 급여 실험군들에서는 체중 증가량이 5% 수준에서 유의적으로 감소하였다. 각 조직 중량은 오르트산 급여군에서 간 조직에서 5% 수준에서 유의적으로 증가하였고 FF-8 투여에 의해 다소 감소하는 것으로 나타났다. 한편, 신장 및 비장에서도 오르트산 급여에 의해 5% 수준에서 유의적으로 감소하였다. 간 조직 중의 과산화지질 농도는 오르트산 급여군에서 5% 수준에서 유의적으로 증가하였고, FF-8 균체 급여군에서 감소하였다. 이때 간 조직 중의 글루타티온 농도도 유사한 경향을 보였다. 천연 항산화 미네랄로 알려진 간 조직 중의 아연 농도는 정상군에 비해 오르트산 유발 지방간에서 감소하였고, FF-8 균체 급여에 의해 다소 증가되는 것으로 나타났다. 이상의 실험 결과에서 오르트산-유발 지방간에서 지질과산화 농도의 증가는 간 조직내 천연 항산화 물질인 글로타티온과 아연 농도의 현저한 감소에 기인하였고, 항산화 물질인 글루타티온을 고함유한 S. cerevisiae FF-8 효모 균체 동시 급여에 의해서는 글로타티온과 아연 농도의 증가에 의해 과산화지질 농도가 경감됨으로서 오르트산 유발 산화스트레스를 경감시키는 효과가 있는 것으로 확인되었다.

• 대한한방내과학회지
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• 제29권1호
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• pp.117-129
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• 2008

Background & Objective : Naeso-san(NSS) has been used for the treatment of functional dyspepsia, regarded as a gastric dysmotility disease. A main cause of gastric dysmotility is antral dilatation or antroduodenal uncoordination. Therefore, we investigated the effect of NSS on gastric motility and its mechanism of action, as well as the morphologic changes in antral dilatated rats. Methods : Antral dilatated rats were induced by wrapping a nonabsorbable rubber ring(D:6mm, W:4mm, T:1mm) around the 1st portion of the duodenum for 8 weeks. Then morphologic changes were investigated and compared with normal intact rats before and after 8 weeks. Gastric emptying was measured by administration of normal saline(NS) or NSS in normal intact and antral dilatated rats. In another series of experiments to evaluate the mechanism of NSS under delayed conditions, normal intact rats were treated with atropine sulfate(1mg/kg, s.c.), quinpirole HCl(0.3mg/kg, i.p.), $NAME(N^{G}-nitro-L-arginine$ methyl ester, 75mg/kg, s.c.) and cisplatin(10mg/kg, i.p.), respectively. The myoelectrical activity of the gastric smooth muscle was recorded in normal intact and antral dilatated rats. The contractile waves were measured for 30 minutes before and after administration of each solution(NS, NSS). Results : Body weight gain of antral dilatated rats was significantly lower than that of the controls. Futhermore, we found the thickness of the mucosal and muscular layers and surface area of the stomach increased significantly compared with controls. NSS 278㎎/㎏ improved gastric emptying more than normal saline or NSS 93mg/kg in normal intact(p=0.026) and antral dilatated rats(p=0.03). NSS enhanced gastric emptying significantly in the NAME treated group(p=0.002). NSS 278mg/kg increased the significant postprandial dominant power than that of NS in normal intact rats, whereas there was no statistical significance in antral dilatated rats. Conclusions : NSS stimulates gastric motility through the cholinergic pathway. We expect that pathologic model with antral dilatation can be used as an exprimental tool which is similar to dyspepsia and NSS would be effective especially in dysmotility-like functional dyspepsia with antral dilatation or impaired reservoir functions such as gastric adaptive relaxation.

• 동의신경정신과학회지
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• 제23권2호
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• pp.99-120
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• 2012

Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.

• Journal of Ginseng Research
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• 제39권2호
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• pp.116-124
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• 2015

Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

• Journal of Acupuncture Research
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• 제23권5호
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• pp.23-29
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• 2006

Objectives : The present study was conducted to evaluate the effects of automatically controlled rotating acupuncture (ACRA) on thermal allodynia in neuropathic pain rats, and to examine whether the endogenous opioid system mediates the effects of ACRA. Methods : For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, ACRA stimulation with 4 different stimulation conditions (i.e., angle and frequency of rotation: 90o+1Hz, 90o+1/4Hz, 360o+/1Hz, and 360o+1/4Hz) was delivered to the Zusanli (ST36) acupoint for 15 min. The behavioral signs of thermal allodynia were evaluated by the tail immersion test (i.e., immersing the tail in cold $(4^{\circ}C)$ or warm $(4^{\circ}C)$ water and measuring the latency to an abrupt tail movement) before and after the stimulation. In an additional set of experiments, we examined the effects of naloxone (opioid Results : ACRA stimulations under all of the conditions above significantly relieved thermal antagonist, 2mg/kg, i.p.) on the action of ACRA stimulation. allodynia. There is no difference in the anti-allodynic effects among the 4 stimulation conditions. In addition, the effect of ACRA on thermal allodynia was reversed by naloxone pretreatment. Conclusion : These results indicate that ACRA stimulations have relieving effects on thermal allodynia in neuropathic pain rats, irrespective of stimulation parameters, and that this is mediated by the endogenous opioid system.

• 한국발생생물학회지:발생과생식
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• 제14권3호
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• pp.199-205
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• 2010

A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD). The present study was undertaken to examine whether depletion of brain dopamine (DA) stores with 6-OHDA can make alteration in the activities of the testicular steroidogenesis in adult rats. Young adult male rats (3 months old) were received a single dose of 6-OHDA (200 ${\mu}g$ in 10 ${\mu}{\ell}$/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. The mRNA levels of steroidogenesis-related enzymes were measured by qRT-PCRs. Serum testosterone levels were measured by radioimmunoassay. Single icv infusion of 6-OHDA significantly decreased the mRNA levels of CYP11A1 (control:6-OHDA group=$1:0.68{\pm}0.14$ AU, p<0.05), CYP17 (control:6-OHDA group=$1:0.72{\pm}0.13$ AU, p<0.05). There were no changes in the mRNA levels of $3{\beta}$-HSD (control:6-OHDA group=$1:0.84{\pm}0.08$ AU) and $17{\beta}$-HSD (control: 6-OHDA group=$1:0.63{\pm}0.20$ AU), though the levels tended to be decreased in the 6-OHDA treated group. Administration of 6-OHDA decreased significantly the mRNA level of StAR when compared to the level of saline-injected control animals (control:6-OHDA group=$1:0.72{\pm}0.08$ AU, p<0.05). Treatment with single dose of 6-OHDA remarkably lowered serum testosterone levels compared to the levels of control group (control:6-OHDA group=$0.72{\pm}0.24:0.13{\pm}0.03ng/m{\ell}$, p<0.05). Taken together with our previous study, the present study demonstrated that the activities of hypothalamus-pituitary-testis hormonal axis could be negatively affected by blockade of brain DA biosynthesis, and suggested the reduced reproductive potential might be resulted in the animals. More precise information on the testicular steroidogenic activities in PD patients and PD-like animals should be required prior to the generalization of the sex steroid hormone therapy to meet the highest standards for safety and efficacy.