• The Korea Journal of Herbology
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• v.35 no.6
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• pp.29-34
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• 2020

Objectives : Gyejigamchoyonggolmoryeo-tang (GT, Guizhigancaolonggumulitang in Chinese) is a herbal medicine to be prescribed for insomnia caused by anxiety induced by Heart-Heat and elevated Liver-Yang. In the present study, the onset time (sleep latency) and the duration time of sleep were measured to find out the sleep inducing effects of GT. The expression of c-fos immunohistochemistry was also measured at the ventrolateral preoptic area (VLPO) and tuberomammillary nucleus (TMN) site in brain. Methods : The onset time (sleep latency) and the duration time of sleep were measured 30 minutes after thiopental sodium injection. Thereafter, brain tissue was obtained and c-fos immunohistochemistry was performed on the VLPO and TMN sites. Results : GT statistically significantly reduced the sleep latency required to enter sleep, and significantly increased sleep duration time. GT significantly increased the number of c-fos immunohistochemical staining-positive cells in the sleep-inducing center (VLPO), whereas GT significantly decreased the number of c-fos immunohistochemical staining-positive cells in the arousal center (TMN). Conclusions : It could be concluded that the GT shortened the sleep latency and increased the duration time for sleep induced by thiopental sodium. And it was confirmed that the mechanism was to stimulate the sleep-inducing center (VLPO) and suppress the arousal center (TMN) in the brain. The results of this study are considered to be useful as scientific evidence that can be used clinically for the treatment of insomnia caused by anxiety.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.97-107
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• 2002

Objective : Acupuncture is a method used to treat many kinds of pain in oriental cultural medicine. Especially when hetero-segmental area acu-points are stimulated, the therapeutic effects of pain control have more critical properties than other methods of acupuncture. However, the mechanism of pain control by acupuncture is contradictory so far. The present study examined the effects of electroacupuncture (EA) applied to the acu-point of the hetero-segmental area on modulation of formalin-induced pain in Sprague-Dawley rats. Methods : In order to apply EA to acu-points in the plantar area of right forepaws, a pair of Teflon-coated stainless steel wires were implanted in HT 7 (Shin-Moon) and PC 7 (Dae-Reung) 7 days before the behavioral test. A behavioral test was performed by means of video camera after injection of 5% formalin ($50{\;}\mu\textrm{l}$) into the lateral plantar region of the left hind paw. EA was delivered by a constant DC current stimulator at 4~5 mA, 2 ms, and 10 Hz for 30 min. c-Fos protein expression was measured in the lumbar spinal cord at 2 hr and 4 hr after formalin injection. Results : Behavioral responses including favoring, flinching and biting occurred in the biphasic pattern, such as the 1st phase (0~5 min) and the 2nd phase (20~45 min) after formalin injection. However, EA (4~5 mA, 2 ms, 10 Hz) significantly inhibited the behavioral responses. Injection of formalin expressed c-Fos protein on the ipsilateral dorsal horn neurons in L3 - L5 and the expression was sustained more than 4 hrs after formalin injection. However, EA decreased c-Fos protein expression at dorsal horn neurons in the lumbar spinal cord till 4hrs after formalin injection. Conclusions : These results suggest that EA modulates formalin-induced pain and this inhibitory action may be elicited by the descending inhibitory system.

• The Journal of Korean Physical Therapy
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• v.16 no.3
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• pp.9-21
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• 2004

The purpose of study is that we will observe the change of c-fos with the immunohistochemistry method and then we will study the effect of micro current stimulation following the frequency after inducing pain to rats with capsaicin. Rat were classified to SD and they have growed for 8 weeks. We classify to four groups, ordinal group is used in experiment I, the group which we induce pain is used in experiment II, the application group which we induce pain and then the high frequency micro current stimulation is used in experiment III, the application group which we induce pain and then the low frequency micro current stimulation is used in experiment IV, we get the following result. Compare with experiment II, experiment III, and experiment IV from acute pain modal in the immunohistochemistry experiment which has c-fos protein as an antigen, c-fos immunoreactive positive neurons significantly after induced pain for two hours(p<0.001). According to these results, from rats induced pain, micro current stimulation effect to reducing pain, but following frequency micro current stimulation theraphy isn't different from immunoreactive c-fos

• Herbal Formula Science
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• v.19 no.1
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• pp.161-174
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• 2011

Objectives : The effects of Extraction after Mixture of Bupleuri Radix and Lycii Radicis Cortex on the change of the HPA-Axis system and the Catecholamic system was investigated. Methods : After performing the Forced Swimming Test(FST), the expressions of corticotropin releasing factor(CRF), c-Fos in the paraventricular nucleus(PVN), and tyrosine hydroxylase(TH) in the ventral tegmental area(VTA) and locus coeruleus(LC) were measured by immunohistochemical method. Results : The duration of immobility in FST was significantly decreased in A 100(Extraction after Mixture of Bupleuri Radix and Lycii Radicis Cortex, 100mg/kg) and A 400(Extraction after Mixture of Bupleuri Radix and Lycii Radicis Cortex, 400mg/kg)(p<0.001). The expression of CRF in the PVN was shown the tendency to reduce in A100 and A400. The expression of c-Fos in the PVN was shown the tendency to reduce in A100 and A400. The expression of TH in the VTA was shown the tendency to reduce mildly in A100 and A400. The expression of TH in the LC was significantly reduced in A400(p<0.001). And the dose dependent reduction tendency was shown, respectively. Conclusions : According to the results above mentioned, the immobility, c-Fos and CRF expression was reduced at lower dose and was increased at higher dose. Therefore there is contradictory effects on the HPA Axis system in accordance with the dose. But in the effects on the catecholaminergic system, it significantly reduced the expression of TH in the LC. It was validated that the effect on the catecholaminergic system was ruled by Bupleuri Radix rather than Lycii Radicis Cortex via mainly the noradernergic system.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.143-158
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• 2011

Objectives : Peripheral nerve injuries are commonly encountered clinical problem and often result in severe functional deficits. The aim of this study is to evaluate the effects of aqueous extract of Achyranthes japonica(AJ) on functional recovery in sciatic nerve after crushed sciatic nerve injury. Methods : In the present study, the animals in the AJ-treated groups received the aqueous extract of AJ at the respective doses orally for 13 consecutive days. In order to assess the effects of the aqueous extract of AJ on function recovery in crushed sciatic nerve injury, sciatic functional index(SFI) was performed. c-Fos expression in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG), and neurofilament, and the expressions of brain-derived neurotrophic factor(BDNF), nerve growth factor(NGF) following crushed sciatic nerve injury in rats were investigated. For this, immunohistochemistry and western blot were performed. Results : In the present study, crushed sciatic nerve injury showed characteristic gait changes showing decrease of SFI value and treatment with the aqueous extract of AJ significantly enhanced the SFI value. Neurofilament expression in the sciatic nerve was decreased by crushed sciatic nerve injury and treatment with the AJ increased neurofilament expression. The expressions of BDNF and NGF in the sciatic nerve were increased following crushed sciatic nerve injury and treatment with the AJ significantly controlled the sciatic nerve injury-induced increment of BDNF and NGF expressions. c-Fos expressions in the PVN and vIPAG were increased following crushed sciatic nerve injury and treatment with the AJ significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions. Conclusions : These results suggest that AJ treatment after crushed sciatic nerve injury is effective in the functional recovery by enhancing axonal regeneration and suppressing of pain.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.275-281
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• 2015

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

• The Journal of Internal Korean Medicine
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• v.24 no.2
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• pp.181-189
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• 2003

The goal of this study is to investigate whether Uncariae Ramulus et Uncus can protect nerve cells against ischemic neuronal damage is caused by middle cerebral artery occlusion (MCAO) in rats' brains and to investigate whether the neuroprotective effect of Uncariae Ramulus et Uncus is concerned with IEGs(immediate early genes) expression. Uncariae Ramulus et Uncus(l00mg/kg) was administered immediately after 2 hours of MCAO and maintained for 7 days. On 7th days after 2 hours of MCAO, the brains of rats were sliced through the hippocampus. c-Fos immunohistochemistry stain and Cresyl violet stain were done for microscopic examination. Each number of viable neurons and c-Fos immunoreactive cells in CA1 was counted. The density of neurons and c-Fos immunoreactive cells were significantly decreased in MCAO-operated ischemic rats compared to that sham-operated rats. Administration of Uncariae Ramulus et Uncus group significantly elevated MCAO-induced decrease in density of neurons, and elevated MCAO-induced decrease in c-Fos immunoreactive cells. These results suggest that the neuroprotective effect of Uncariae Ramulus et Uncus against focal cerebral ischemia. Also, we hypothesized that neuroprotective mechanism of Uncariae Ramulus et Uncus is related to IEGs expression.

• International Journal of Oncology
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• v.56 no.2
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• pp.630-640
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• 2020

Plant flavonoid 2',3,4',5,7-pentahydroxyflavone (morin hydrate), isolated from the family Moraceae (Morus alba L.), is known to have anti-inflammatory and anticancer effects. However, its pharmaceutical effects on metastasis have not been fully elucidated to date. Therefore, the current study investigated the effects of morin hydrate on cancer metastasis in MCF-7 human breast cancer cells. The results showed that morin hydrate suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion via the inhibition of matrix metalloproteinase (MMP)-9 activity. Furthermore, gene expression level of MMP-9, MMP-7, urokinase plasminogen activator (uPA), uPA receptor (uPAR) and fibronectin were significantly decreased by morin hydrate treatment. Morin hydrate inhibited the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β, and downregulated the expression of an activator protein-1 subunit c-Fos. In addition, the GSK-3β phosphorylation and c-Fos expression were suppressed by PI3K/Akt pathway inhibitors, LY294002 and wortmannin. Taken together, these results demonstrated that morin hydrate reduced the metastatic potential in TPA-treated MCF-7 human breast cancer cells via the inhibition of MMPs, uPA and uPAR, and the underlying Akt/GSK-3β/c-Fos pathway. Therefore, the present investigation suggested that morin hydrate may be a natural substance with a preventive potential for metastasis in breast cancer cells.

• Science of Emotion and Sensibility
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• v.10 no.3
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• pp.411-418
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• 2007

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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.220-225
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• 2002

To determine the anti-stress effect of KCG(加味天麻鉤藤飮) extract on sprague-dawley rats. we conducted a research about the change of weight, activity, reactivity, c-fos protein, cytotoxicity against PC12 cell line and heal shock protein. 1) KCG extract siginificantly inhibited the decrease of body weight induced by stress, compared with the control group. 2) KCG extract had no siginificant effect in the activity and reactivity of rats between the control and the experimental groups. 3) KCG extract siginificantly restrained c-fos protein manifestation, compared with the control group. 4) KCG extract siginificantly restrained heat shock protein, compared with the control group. These results suggested that KCG might be usefully anti-stress effect.