• The Journal of Korean Medicine
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• v.24 no.2
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• pp.204-212
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• 2003

Current therapy for acute ischemic stroke is highly focused on neuroprotective agents, and many herbal medicines have been challenged for experimental models. The aim of this study is to investigate whether Angelicae gigantis Radix can protect nerve cells against ischemic neural damage of middle cerebral artery occlusion (MCAO) in rats' brains. Rats were treated with Angelicae gigantis Radix immediately after 2 hours of MCAO for 7 days. On the 7th day, the brains of the rats were sliced through the hippocampus and dyedby c-Fos immunohistochemistry stain and cresyl violet stain for microscopic examination. The number of viable neurons and c-Fos immunoreactive cells in CA1 regions was counted. MCAO caused significant decrease in density of neurons and c-Fos immunoreactive cells compared to those of sham-operated rats. Administration of Angelicae gigantis Radix significantly elevated MCAO-induced decrease in density of neurons and c-Fos immunoreactive cells. These results suggest that the neuroprotective effect of Angelicae gigantis Radix against focal cerebral ischemia is related to c-Fos gene expression. Thus, these findings indicate that Angelicae gigantis Radix can be used for treatment and prevention of cerebral ischemia.

• Korean Journal of Oriental Medicine
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• v.9 no.1
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• pp.157-178
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• 2003

Objective : This study was designed to assess the protective effects of Chengwhabosimtang on the animal model of depression, chronic mild stress(CMS). Method : Male Sprague-Dawley rats Were used for this experiment. The subjects Were divided into 3 groups (1. CMS-drug: Chengwhabosimtang administered during CMS treatment, 2. CMS-vehicle: water administered, 3. normal ). After 4 weeks of CMS treatment they were executed Forced swimming test(FST) and Elevated plus maze. Tyrosine hydroxylase(TH) in ventral tegmental area(VTA) and c-Fos in paraventricular nucleus(PVN) were measured. Result : 1. In FST, CMS-drug group showed significantly decreased immobility behavior. 2. CMS-drug group showed no significantly lower TH level in VTA than CMS-vehicle group. 3. CMS-drug group showed significantly less c-Fos expressed cell bodies in PVN than CMS-vehicle group. 4. In Elevated plus maze, CMS-drug group showed no significantly anxiety. Conclusion : These results suggest that Chengwhabosimtang may have protective antidepressant effects in CMS model rats. And these effects could be explained by the elevated stress-copying behaviors which are related with PVN of hypothalamus and dopaminergic neurons in VTA.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.137-149
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• 2006

Objective : The purpose of this study is to investigate the effect of Radix Scutellariae on repeated nicotine-induced locomotor activity and c-Fos expression utilizing Fos-like immuno-histochemistry method in the nucleus accumbens, and the striatum, one of the major projection areas of the control DA system. Methods : Male Sprague-Dawley rats were divided into untreated(normal), nicotine-treated (control), Radix Scutellariae-treated(sample) groups, RS group received Radix Scutellariae(100mg/kg, i.p.) 30minutes before injection of nicotine(0.4mg/kg, s.c.) for 7days. Rat were followed withdrawal for 3 days and one challenge for 1day. Results : Systemic challenge with nicotine produced a much larger locomotor activity and expression of c-Fos in the nucleus accumbens and the striatum. Pretreatment with Radix Scutellariae decreased in nicotine-induced locomotor activity and c-Fos expression in the core, shell, straitum area. Conclusion : These results demonstrated that reduction in locomotor activity by Radix Scutellariae may be mediated by reduction of dopamine release and of postsynaptic neuronal activity in striatum, the nucleus accumbens. Out results show neurochemical evidence for the biological effects of Radix Scutellariae that ultimately may help us to understand how Radix Scutellariae can be used to treat nicotine addiction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.549-552
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• 2003

To investigate the protective effect of Sophorae Radix (SR) on the damage by pulmonary vascular endothelial cells by xanthine oxidase (XO)/hypoxanthine (HX)-induced oxygen tree radical, Neutral Red (NR) and c-fos immunopositive cell assay were used. The results were obtained as follows ; The viability of vascular endothelial cells treated with XO/HX was decreased. And c-fos immunopositive cells represented a maximal increase in group treated with XO/HX for 2 hour in pulmonary vasvular endothelial cells. But pretreated groups with SR extracts were not inhibited the increase of c-fos immunopositive cells by XO/HX in a dose-dependent manner. These results show that XO/HX elicits toxic effects in cultured pulmonary vascular endothelial cells, and suggest that SR extract is very effective in the prevention of XO/HX-induced increase of c-fos immunopositive cells.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.115-120
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• 1996

To investigate characteristic drug effects on the genetic basis, the authors administered haloperidol- the $D_2$ antagonist- and clozapine -the atypical antipsychotics with few extra- pyramidal side effects- to the rats. Then, we edobtain brain specimen from the striatum, prefrontal cortex, and cortical region and compared the degree of c-fos expression. The results are 1) haloperidol was found to produce a rapid and transient induction of dos mRNA expression in striatum as compared with cortex and prefrontal area. 2) clozapine was found to produce rapid induction of c-fos mRNA in striatum and prefrontal area. From these data, we can concluded that the mechanism of action of haloperidol is different from the mechanism of clozapine in gene expression.

• Korean Journal of Acupuncture
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• v.26 no.4
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• pp.195-209
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• 2009

Objectives : Transient inflammation has been demonstrated to alter visceral sensory function in animal models and acute mucosal inflammation may precede the manifestation of visceral hyperalgesia. Thus in this study we compared effects of herbal acupuncture of Nidus Vespae (NV) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods : In Male Sprague-Dawley rats, weighing 250 ~ 400 g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Under general anesthesia, acupoints of LI4 (Hapkok), SI25 (Cheonchu), ST36 (Joksamni), BL25 (Daejangsu) were intramuscularly injected by NV. Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hrs after TNBS induced colitis by immunohistochemistry. Results : The expression of c-Fos protein in L6 s.c., Sol, LC and PAG increased 24 hrs after TNBS injection into colorectum as compared to normal group. NV herbal acupuncture also inhibited the expression of c-Fos protein in Sol but not L6 s.c., LC, and PAG. NV to ST36 inhibited significantly the c-Fos expression in Sol and PAG. NV to ST25 inhibited the c-Fos protein expression all over the observation area. NV to BL25 showed the inhibitory effects in the areas except LC. Whether or not a role of endogenous opioids, intrathecal injection of naltrexone (30 ug / 30 ul) was applied before the 2nd herbal acupuncture treatment 24 hrs after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem under different conditions such as type of herbal acupuncture compound and choice of acupoint. Conclusions : In summary, these data show that herbal acupuncture of NV inhibits signal pathways such as spinal cord and brain stem ascending hypersensitivity of colorectum after TNBS induced colitis. This effect may be mediated by acupoints through the endogenous opioid system involving the pain modulation.

• BMB Reports
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• v.32 no.6
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• pp.594-598
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• 1999

The Jun and Fos families of eukaryotic transcription factors form heterodimers capable of binding to their cognate DNA enhancer elements. We are interested in searching for inhibitors or antagonists of the binding of the Jun-Fos heterodimer to the activator protein-1 (AP-1) site. The basic-region leucine zipper (bZIP) domain of c-Fos was expressed as a fusion protein with glutathione S-transferase, and allowed to form a heterodimer with the bZIP domain of c-Jun. The heterodimer was bound to glutathione-agarose, to which were added radiolabeled AP-1 nucleotides. After thorough washing, the gel-bound radioactivity was counted. The assay is faster than the coventional electrophoretic mobility shift assay because the gel electrophoresis step and the autoradiography step are eliminated. Moreover, the assay is very sensitive, allowing the detection of picomolar quantities of nucleotides, and is not affected by up to 50% dimethylsulfoxide, a solvent for hydrophobic inhibitors. Curcumin and dihydroguaiaretic acid, recently known inhibitors of Jun-Fos-DNA complex formation, were applied to this Jun-GST-fused Fos system and revealed to decrease the dimer-DNA binding.

• Herbal Formula Science
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• v.19 no.2
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• pp.39-46
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• 2011

Objectives : The BangPungTongSungSan(BPTSS) has been used as a therapeutic agent for cerebrovascular disease, cerebral hemorrhage, hypertension, diabetes and obesity in oriental medicine. The present study designed to investigate the effect of BPTSS on behavioral change and neuronal activation induced by acute methamphetamine(METH, 2 mg/kg, i.p.) in C57BL/6 mice. Methods : Mice received the oral administration of BPTTS(25, 50 and 100 mg/kg) 1 h prior to saline or METH administration. Locomotor activity was measured for 90 min using videotractking method and c-Fos expression, as marker of neuronal activation, was identified in a separate groups of mice by immunohistochemistry. Results and conclusions : Methamphetamine injection significantly increased locomotor activity and c-Fos expression in the nucleus accumbens and striatum. Interestingly, BPTTS(100 mg/kg) significantly suppressed locomotor activity and c-Fos expression in the nucleus accumbens and striatum by acute exposure to METH. These results suggest that BangPungTongSungSan may be effective in suppressing the reinforcing effect of methamphetamine by modulation neuronal activity.

• Korean Journal of Acupuncture
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• v.19 no.1
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• pp.25-33
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• 2002

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. Injections of cocaine can produce one of the immediate-early gene, c-fos expression in the brain and behavioral activation. Acupuncture as a therapeutic intervention is widely used for the treatment of many mental disorders such as drugs of abuse. In order to investigate whether acupuncture has an influence on cocaine-induced reinforcing and behavioral effects, we examined the effect of acupuncture on cocaine-induced locomotor activity and c-Fos expression in the nucleus accumbens and the striatum using Fos-like-immunoreactivity(FLI). Male SD rats received acupuncture for 1 min after injection of cocaine hydrochloride(1 mg/kg, i.v.). The employed acupuncture point, Shenmen$(HT_7)$, has been clinically used to treat mental and psychosomatic disorders. Injections of cocaine produced a marked increase in locomotor activity and FLI in the nucleus accumbens and the striatum. Acupuncture at $HT_7$, but not at control points($PC_6,\;TE_4$ or tail), significantly attenuated cocaine-induced increase in locomotor activity and Fos-like immunoreactivity. These results demonstrated that reduction in locomotor activity by acupuncture may be reflected by reduction of postsynaptic neuronal activity in the nucleus accumbens and the striatum. Our results suggest that acupuncture may have a therapeutic effect on cocaine addiction.