흰쥐의 Adjuvant 유발 다발성 관절염에 대한 마황 약침의 치료 효과

이한창,염미정,김건호,심인섭,최강덕,이혜정,함대현 대한동의생리학회,대한동의병리학회 2003 동의생리병리학회지 Vol.17 No.2

The current studies investigated the therapeutic effects of Ephedra sinica Stapf (ES) herb-acupuncture on the inflammatory responses of rat arthritic joint, which was induced by the intradermal injection of heat-killed Mycobacterium tuberculosis emulsified in squalene to the base of the tail. The measurements of body weight and articular index were exploited as the assessment methods addressing arthritic symptoms, and the expression profiles of cytokines such as TNF-α, IL-1β and IL-6 in the, rat joint were analyzed using RT-PCR. The articular indexes of arthritic rats were significantly restored after the treatment with ES herb-acupuncture. Although the clinical symptoms of arthritic rats were apparently alleviated by the ES treatments, their body weights were not recovered. It maybe due to the weight-loss and energy enhancement effects of ES extracts. The expression of TNF-α, IL-1β and IL-6 enes, which were highly stimulated in the knee joints of arthritic rats, were restored to the levels of normal rats after the ES treatment. The therapeutic effect of ES herb-acupuncture was not observed in ES-treated, non-acupoint arthritic group as a sham control. The ES herb-acupuncture into an acupoint ST36 was found to be effective in alleviating the arthritic symptoms in adjuvant-induced arthritis rats as regards the body weight, joint appearance and the expression profiles of inflammatory cytokines.

인체 간 Microsome에서의 우슬 추출물의 Cytochrome P450 약물 대사효소에 대한 억제작용

김경아,이지숙,박히준,김진우,김창주,심인섭,한승무,임사비나 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Objective : Achyranthes bidentata radix (Usul) has been used as anti-arthritic, antiallergic, antidiuretic and so on Recently extracts of Achyranthes bidentata radix have shown anti-inflammatory and cancer preventive effects in vitro and in vivo. Methods : We therefore evaluated the inhibitory potential of ehtanol extracts of Achyranthes bidentata radix on cytochrome P450(CYP) isoforms-catalyzecd reactions, which relate to causes of cancer and inflammation, including CYP1A2, CYP2C9, CYP2C19, CYP2E1, CYP2D6, CYP2C8, and CYP3A4, using human liver microsomal preparations. Results : The extracts showed weak or negligible inhibitory effects on CYP2C9-catalyzed (S)-warfarin 7-hydroxylation, CYP2C19-catalyzed S-mephenytoin 4-hydroxylation, and CYP2D6-catalyzed dextromethorphan O-demethylation with each IC50 over 1750 g/㎖, respectively. However, it showed relatively significant inhibitory effect on CYP1A2-catalyzed phenacetin O-deethylation and CYP2E1-catalyzed chloizoxazone 6-hydroxylation with IC50s of 970.5 g/㎖ and 821.4 g/㎖, respectively. Conclusions : These results suggest that extracts of Achyranthes bidentata radix have inhibitory effects on CYP-catalyzed reactions, expeciallyCYP1A2 and CYP2E1, in human liver microsomes. These effects appear to relate to anti-inflammatory and cancer prevention following decrease of reactive oxygen species formed by CYP, especially CYP1A2 and CYP2E1, by Achyranthes bidentata radix. However, further evaluation is necessary to demonstrate and to confirm its effects in human.

Effect of the Electroacupuncture at ST36 in TMT-induced Memory Deficit Rats

Shim, Hyun-Soo,Park, Hyun-Jung,Lee, Hye-Jung,Shim, In-Sop The Physiological Society of Korean Medicine and T 2011 동의생리병리학회지 Vol.25 No.4

In order to the neuroprotective effect of electroacupuncture (EA), the present study examined the effects of electroacupuncture inacupoint ST36 (Stomach 36) on trimethyltin chloride (TMT)-induced cognitive impairments rat using the Morris water maze (MWM) task and immunohistochemistry staining. The rats were randomly divided into the following groups: naive rat (Normal), TMT injection rat (Control), TMT injection + EA treated rat inacupoint ST36 (ST36) and TMT injection + EA treated rat in non-acupoint, base of tail (Non-AC). Electroacupuncture (2Hz, 2mA, and 10 minutes)was applied either to the acupuncture point ST36 or the nonacupuncture point in the tail for the last 14 days. In the water maze test, the animals were trained to find a platform in a fixed position during 4d and then received 60s probe trial on the $5^{th}$ day following removal of platform from the pool. Rats with TMT injection showed impaired learning and memory of the tasks and treatment with EA in acupoint ST36 (P<0.05) produced a significant improvement in escape latency to find the platform after $2^{nd}$ day and retention trial in the Morris water maze. Consistent with behavioral data, treatment with EA in acupoint ST36 also significantly increased expression of Choline acetyltransferase (ChAT) and Acetylcholinesterase (AChE) immunoreactive neurons in the hippocampus compared to the Control group. These results demonstrated that EA in acupoint ST36 has a protective effect against TMT-induced neuronal and cognitive impairments. The present study suggests that EA in acupoint ST36 might be useful in the treatment of TMT-induced learning and memory deficit.

Modulatory effect of ginseng total saponin on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the rat

Shim, In-Sop,Won, Je-Seong,Lee, Jin-Koo,Song, Dong-Keun,Kim, Sang-Eun,Huh, Sung-Oh,Kim, Yung-Hi,Suh, Hong-Won 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2000 No.-

Several studies have demonstrated that behavioral activation induced by psychostimulants is prevented by ginseng total saponin (GTS), which has been known to act on the central dopaminergic system. In an attempt to investigate whether the effect of GTS is through its inhibitory action on the elevated dopaminergic transmission, we examined the effect of GTS on nicotine-induced dopamine (DA) release in the nucleus accumbens (NA) of freecly moving rats using in vivo microdialysis. Systemic injection of nicotine (3 mg/kg; 1.p.) produced a mild increase in extracellular DA of dialysates samples in the NA (132 ± 13% over basal levels at the peak). GTS(100 mg/kg; i.p.) had no effect on resting levels of extracelluar DA. However, an increase in accumbens DA release produced by systemic nicotine was completely blocked by systemic pre-treatment with GTS (100 mg/kg; i.p.). In addition, the effect of GTS on nicotine-induced tyrosine hydroxylase (TH) and immediate early gene expression in ventral tegmental area (VTA) or NA regions was examined. A single injection of nicotine increased TH mRNA level at VTA region. GTS, which did not affect the basal TH mRNA expression, attenuated nicotine-induced TH mRNA expression. Nicotine slightly increased both c-fos and c-jun mRNA level and GTS, which did not affect the basal c-fos and c-jun mRNA expression, further enhanced nicotine-induced c-fos and c-jun mRNA level at both VTA and NA regions. Our results suggest that FTS may have an inhibitory action against nicotine-induced DA release in NA region and TH mRNA expression in VTA region. GTS may exert an potentiative effect on both c-fos and c-jun mRNA expression at NA region through inhibiting the release of DA in NA. ⓒ 2000 Elsevier Science Ireland Ltd. All rights reserved.

흰쥐에서 저주파소음에 의한 스트레스 반응

최웅기 ( Woong Ki Choi ),이규섭 ( Kyu Sop Lee ),정혜영 ( Hye Young Joung ),이영창 ( Young Chang Lee ),손진훈 ( Jin Hun Sohn ),이배환 ( Bae Hwan Lee ),변광호 ( Kwang Ho Pyun ),심인섭 ( In Sop Shim ) 한국감성과학회 2007 감성과학 Vol.10 No.3

저주파소음(low frequency noise; LFN)은 인체의 다양한 기관과 정신적 상태에 영향을 미치며, 진동음향질환(vibroacoustic disease; VAD)같은 질병들을 야기 시킨다. 이전의 연구에서는 인간 또는 설치류에서 VAD는 우울증 또는 불안장애와 같은 만성적인 정신 건강에 위험을 미친다고 보고되고 있다. 본 연구에서는 LFN이 스트레스의 신경생리적 반응에 미치는 영향을 규명하고자 하였다. 이를 위하여, LFN에 노출된 흰쥐에서 스트레스 반응에 중요한 역할을 하는 paraventricular nucleus of the hypothalamus(PVN)에서 초기발현유전자인 c-fos 양성세포 발현, locus coeruleus(LC)에서 NE 생성 효소인 tyrosine hydroxylase(TH) 양성세포 발현과 스트레스 호르몬의 농도를 측정하였다. LFN 집단은 각각 32.5Hz 와 125Hz를 하루에 4시간씩 이틀 동안 소음에 노출 하였으며, 정상집단은 소음에 노출되지 않도록 하였다. 저주파소음에 노출 후 집단 간 혈액내 코르티코스테론 분석과, 면역조직염색법을 이용하여 스트레스에 반응하는 PVN에서 c-fos발현과, LC에서 TH를 분석한 결과, PVN에서는 c-fos의 발현과 LC에서 TH의 발현이 증가됨을 관찰할 수 있었으며, 그리고 혈중 코르티코스테론의 농도 또한 LFN집단에서 높게 발현됨을 확인 하였다. 그리고 32.5Hz 보다 125Hz의 소음에서 면역염색반응과 코르티코스테론의 결과가 다소 높게 나타남을 알 수 있었다. 이러한 결과는 저주파소음에 의해 스트레스와 연관된 뇌의 부위에서 c-Fos와 TH의 발현이 증가됨을 증명하고 있다. 따라서 저주파소음은 일반적인 스트레스에 의한 반응과 비슷한 신경적 특징들을 보여주고 있다. 그리고 저주파소음에 의한 중추, 말초신경계의 활성화는 아마도 진동음향질환과 같은 행동장애 질병과 관련이 있을 것임을 시사한다. Exposure to low frequency noise(LFN) can lead to vibroacoustic diseases(VADs), which include a systemic disease with lesions in a broad spectrum of organs and a psychiatric condition. It is known that VAD is an established risk factor for the development of many psychological conditions in humans and rodents, including major depression and anxiety disorder. The present study investigated the effects of LFN on neuronal stress responses in the rat brain. The neuronal expression of the proto-oncogene c-fos in the paraventricular nucleus(PVN) of the hypothalamus and tyrosine hydroxylase(TH) in the LC was observed. The immunocytochemical detection of the Fos protein and TH has been used as a marker of neuronal activation in response to stress. In addition, corticosterone concentration was evaluated by using an enzyme-linked immunosorbent assay(ELISA) The LFN groups were exposed to 32.5Hz and 125Hz of noise(4hr/day for 2days). The numbers of c-fos and TH-immunoreactive cells in the PVN and LC were significantly increased in the LFN groups(32.5Hz and 125Hz) compared to the normal group. Corticosterone concentration in plasma was also increased in LFN groups. The present results demonstrated that exposure with LFN produced a pronounced increase in expression of c-Fos and TH in stress-relevant brain areas. These results suggest that the neural characteristics involved in LFN are similar to those activated by typical processive stressors. These results also suggest that the central and peripheral activations by LFN may be related to LFN-related negative behavioral dysfunctions such as VADs.

Effect of Ginsenoside Re on Depression- and Anxiety-Like Behaviors and Cognition Memory Deficit Induced by Repeated Immobilization in Rats

( Bom Bi Lee ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.5

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stressinduced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced openarm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

족삼리(足三里) 시술(施術)된 죽력(竹瀝) 약침(藥鍼)이 Intraluminal Filament 삽입술(揷入術)에 의하여 유발(誘發)된 백서(白鼠)의 허혈성(虛血性) 국소(局所) 뇌손상(腦損傷)에 미치는 영향(影響)

윤대환 ( Dae Hwan Youn ),이봄비 ( Bom Bi Lee ),심인섭 ( In Sop Shim ),나창수 ( Chang Su Na ) 대한경락경혈학회 2005 Korean Journal of Acupuncture Vol.22 No.2

Objectives Bambusae Caulis in Liquamen(BCL) has been used to medication for early stroke in the Oriental Medicine. So this study was planned to investigate the effects of BCL on the focal ischemia-induced by intraluminal filament insertion in the rats. Materials and methods: The focal ischemia was induced by Intraluminal Filament insertion into middle cerebral artery. BCL herbal acupuncture at ST36 was carried out during 3 weeks after focal ischemia-induced. Eight-arm radial maze was used for the behavioral task and neuroprotective effect of BCL acupuncture was observed by Cresyl violet, AchE, ChAT-stain. Results: The error rate in the eight-arm radial maze task was significantly decreased in BCL1 (0.89mg/kg) herbal acupuncture group compared to control group on 3,4,5days, compared to saline acupuncture group on 3,5days. The rate of correct choice was significantly increased in saline acupuncture, BCL1 herbal acupuncture group, BCL2(0.089mg/kg) herbal acupuncture groups compared to control group. The density of neurons in the hippocampal CA1 was the most increased in BCL1 herbal acupuncture group compared to the others. The density of AchE in the hippocampal CAl was significantly increased in BCL1 herbal acupuncture, BCL2 herbal acupuncture groups compared to control group, and in BCL2 herbal acupuncture groups increased compared to saline acupuncture, control groups. The density of ChAT in the hippocampal CA1 was significantly increased in BCL1 herbal acupuncture group compared to saline acupuncture, control groups. Conclusions: These results suggest that BCL herbal acupuncture could be used as a medication for controlling the early stroke.

Bupleurum falcatum Prevents Depression and Anxiety-Like Behaviors in Rats Exposed to Repeated Restraint Stress

( Bom Bi Lee ),( Hye Yeon Yun ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.3

Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxietylike behaviors and alters the expression of corticotrophinreleasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamicpituitary- adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.

지방식이로 유도된 비만동물모델에서의 약침의 효과

김지현,박창신,함대현,이혜정,심인섭,Kim, Ji-Hyun,Park, Chang-Shin,Hahm, Dae-Hyun,Lee, Hye-Jung,Shim, In-Sop 대한약침학회 2004 Journal of pharmacopuncture Vol.7 No.1

Acupuncture has fairly good weight-reducing effect in treating simple obesity due to the neuroendocrine regulation. In this study, the antiobesity effects of herbal acupuncture(HA) with Sang-hwang(phellinus linteus) at Fuai(SP16) were investigated in the rat fed on high-fat(HF) diet. Sang-hwang mushroom has been proven to have anti-carcinogenic effects and Sang-hwang extracts are highly effective in treatment and preventive treatment of AIDS, diabetes and high blood-pressure. To determine whether the Sang-hwang herbal acupuncture may have the anti-obesity effect, male Sprague-Dawley(4-wk-old) rats were fed a HF diet for 5 wk, which produced significant weight gain compared to rats were fed a normal diet, and then herbal acupuncture were treated for 3 wk in HF diet group. The body weight, food consumption, food effeciency ratio(FER), body fat mass, plasma nitric oxide(NO) were investigated in rats fed on normal diet, HF diet, and HF diet with HA(HF-diet-HA) groups. NO has been proposed to be involved in the regulation of food intake. In addition, the expression of appetite peptides such as orexigenic peptide neuropeptide Y(NPY) and the anorectic peptide cholecystokinin(CCK) were observed in the hypothalamus. HF-HA group reduced body weight gain, FER, body fat contents and NO concentration compared to HF diet group. The expression of NPY was reduced in arcuate nucleus(ARC), and CCK was increased in the paraventricular nucleus(PVN) after treatment of HA. In conclusion, Sang-hwang HA reduced adipocity, plasma NO and hypothalamic NPY, but increased CCK expression in the HF dietinduced obesity rat, therefore HA may have anti-obesity action through regulating body weight and appetite peptide of the central nervous system.

Wild Ginseng Attenuates Repeated Morphine-Induced Behavioral Sensitization in Rats

( Bom Bi Lee ),( Sun Oh Kwon ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.7

Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.