• The Korea Journal of Herbology
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• v.26 no.2
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• pp.59-66
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• 2011

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p<0.05~p<0.01). CRF expressions at PVN was significantly decreased in A400(p<0.05).No other group showed significant difference in expression of c-Fos at PVN comparing with control group. TH expressions at VTA was significantly decreased in A100 and A400, respectively(p<0.001). TH expressions at LC was significantly decreased in A100(p<0.01). Conclusions : According to the above results, Mixture of Lycii Radicis Cortex and Moutan Cortex has antidepressant effects via the reduction of CRF expression and the Catecholamine System activity.

• Korean Journal of Biological Psychiatry
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• v.11 no.1
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• pp.14-25
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• 2004

The current understanding of the mechanisms of pharmacotherapy for depression is characterized by an emphasis on increasing synaptic availability of serotonin, noradrenaline, and possibly dopamine, while minimizing side effects. The acute effects of current available effective antidepressants include blocking selective serotonin or noradrenaline reuptake, alpha2 autoreceptors or monoamine oxidase. Although efficacious, current treatments often produce partial or limited symptomatic improvement rather than remission. While current pharmacotherapies target monoaminergic systems, distinct neurobiological underpinnings and other systems are likely involved in the pathogenesis of depression. Recently, several promising hypotheses of depression and antidepressant action have been formulated. These hypotheses are largely based on dsyregulation of neural plasticity, CREB, BDNF, corticotropin-releasing factor, glucocorticoid, hypothalamic-pituitary adrenal axis and cytokines. Based on these new theories and hypotheses of depression, a number of new and novel agents, including corticotropin-releasing factor antagonists, antiglucocorticoids, and substance P antagonists show a considerable promise for refining treatment options for depression. In this article, the current available pharmacotherapies, current understanding of neurobiology and pathogenesis of depression and new and promising directions in pharmacological research on depression will be discussed.

• Korean Journal of Biological Psychiatry
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• v.10 no.1
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• pp.62-69
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• 2003

Corticotropin-releasing factor(CRF) and neuropeptide Y(NPY) are known to play important roles in mediating stress responses and stress-related behavior. To elucidate the role of neuropeptides in response to the condition that had paired with traumatic event, we observed the changes of CRF and NPY by immunohistochemistry using a conditioned footshock paradigm. Male Sprague-Dawley rats were placed in a shuttle box and exposed to 20 pairings of a tone(< 70dB, 5sec) followed by a footshock(FS, 0.8mA, 1sec) over 60min. A second group was exposed to the tone-footshock pairings, returned to the homecage for 2days, and then reexposed to the test chamber and 20tones alone for 60min, prior to sacrifice. Control groups were : a) sacrificed without exposure to FS ; b) exposed to the tone-footshock pairings and then sacrificed two days later ; or c) exposed to the chamber and tones alone, returned to the homecage for 2days and then reexposed to the chamber and 20tones over 60min prior to sacrifice. CRF was increased in animals exposed to FS or the aversive condition(context and tone) that had paired to FS in bed nucleus of the stria terminalis (BNST) compared to the control. NPY was increased by FS in amygdala and PVN, but the condition previously associated with FS results in slight increase only in amygdala area. These results suggest that the BNST appears to be the mostly involved neural circuit in response to explicit cues previously paired with footshock. Moreover, this study raise the possibility that increased CRF peptide in the BNST in response to re-exposure to the aversive condition may underlie, in part, the experience of conditioned fear-related anxiety behavior.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.11
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• pp.640-647
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• 2016

By minimizing fluorescence interference phenomena, aequorin-based luminescence technology can provide a relatively sensitive detection platform with integration of $G{\alpha}16$ protein in order to track internal calcium mobilization by G protein-coupled receptors (GPCR). In this type of cell-based functional assay format, it is essential to optimize the transfection process of a receptor and $G{\alpha}16$ protein. For this study, corticotropin releasing factor receptor subtype 2(CRF2) was set as a model system to generate three stable cells with CRF2 and $G{\alpha}16$ in addition to transiently transfected cells under three different conditions. Agonist (sauvagine) and antagonist (K41498) responses in those cells were analyzed to develop the optimum transfection process. As a result, the effective signal ratio in the dose response experiments of sauvagine and K41498 were at least 10-fold higher (z'=0.77) in CRF2-$G{\alpha}16$ stable cells. For the transient transfection cells, stable expression of $G{\alpha}16$ prior to the CRF2 represented a two-fold higher signal (z'=0.84) than the other cases of transient transfection. In conclusion, for the utilization of transient transfection processes to develop a cell-based GPCR functional assay system, it is suggested to introduce various target receptors after stable expression of $G{\alpha}16$ protein.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.413-421
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• 2014

Corticotropin-releasing factor (CRF) is involved in the stress response and there is increasing evidence that stress influences skin disease such as hair loss. In cultured human hair follicles, CRF inhibits hair shaft elongation, induces premature regression and promotes the apoptosis of hair matrix keratinocytes. We investigated whether CRF influences the dermal papilla cells (DPC) that play pivotal roles in hair growth and cycling. Human DPCs were treated with CRF, adrenocorticotropic hormone (ACTH) and cortisol, key stress hormones along the hypothalamic-pituitary -adrenal (HPA) axis for 1-24 h. Interestingly, CRF modulated the expression of cytokines related to hair growth (KGF, Wnt5a, $TGF{\beta}-2$, Nexin) and increased cAMP production in cultured DPCs. CRF receptors were down-regulated by negative feedback systems. Pretreatment of CRF receptor antagonists or protein kinase A (PKA) inhibitor prevented the CRF-induced modulation. Since the CRF induces proopiomelanocortin (POMC) expression through the cAMP/PKA pathway, we analyzed POMC mRNA. CRF stimulated POMC expression in cultured human DPCs, yet we were unable to detect ACTH levels by western blot. These results indicate that CRF operates within DPCs through CRF receptors along the classical CRF signaling pathway and CRF receptor antagonists could serve as potential therapeutic and cosmetic agents for stress-induced hair loss.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.43 no.4
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• pp.281-287
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• 2017

Stress in skin plays a significant role in both the direct/indirect regulation of cellular processes occurring in hair, which in turn affect the hair cycle. However, experimental data regarding the effects of stress-related corticotropin releasing factor (CRF) released by stress on the apoptotic process involved in hair is limited. Therefore, we investigated the acceleration of early-stage apoptosis induced by atopy-related stress using a 2,4-dinitrochlorobenzene NC/Nga mice model. Expression of CRF, its related proteins, annexin V, and mitochondrial dysfunction were measured by immunohistochemical analyses. Atopic stress strongly stimulated stress hormones response, such as CRF and adrenocorticotropic hormone, in outer epithelial sheath of the hair. Moreover, its stress induced mitochondrial damage and early-stage apoptosis of cells in hair root. These findings suggest that hair damage due to apoptosis in atopy model is accelerated in a high CRF environment. Importantly, the effect of stress-related CRF on apoptosis processes involved in atopy dermatitis-related hair loss, suggests that the CRF-regulating development or maintenance materials may provide effective therapeutic strategies for hair health.

• Animal Bioscience
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• v.35 no.8
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• pp.1235-1249
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• 2022

Objective: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. Methods: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. Results: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor β. Conclusion: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.

• The Korea Journal of Herbology
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• v.25 no.4
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• pp.61-67
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• 2010

Objectives : For the purpose of verifying the anti-depressant effect of Paeoniae Radix Rubra(PR), the expression of corticotropin-releasing factor(CRF), c-Fos and tyrosine hydroxylase(TH) was evaluated after performing the Forced Swimming Test(FST). Methods : Spraque-Dawley rats were ingested PR extract(100mg/kg, 400mg/kg, p.o.) for 3 times prior to FST. And the expression of corticotropin-releasing factor(CRF), c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coelureus(LC) and ventral tegmental area(VTA) was measured immunohistochemically after FST. Results : The duration of immobility was significantly decreased in PR 100mg/kg Group and PR 400mg/kg Group, in comparison with the control group (p<0.001). The expression of CRF in the PVN was significantly decreased in PR 400mg/kg Group in comparison of the control group (p<0.05). The expression of c-Fos in the PVN was rather significantly increased in PR 100mg/kg Group in comparison with the control group, while almost no change was demonstrated in PR 400mg/kg Group. The expression of TH was significantly decreased in VTA in comparison with the control group (p<0.05), but the number of expression cells in LC was slightly decreased in case of PR 100mg/kg group while it was increased in case of PR 400mg/kg Group. Conclusion : Judging from the result of the aforementioned tests, Paeoniae Radix Rubra has decreased immobility. In addition, it has also decreased the expression of CRF and the expression of TH in VTA, while the expression of c-Fos and of TH in LC has no significance. Therefore, it is believed that Paeoniae Radix Rubra has an anti-depressant effect by decreased immobility through the reduced expression of CRF and TH in VTA.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.11
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• pp.1529-1535
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• 2000

The aim of the present study was to determine whether brain corticotropin-releasing factor (CRF) and a new peptide, urocortin (UCN) have a direct action in brain mechanisms controlling feed, water and salt intake in sheep. We gave a continuous intracerebroventricular (ICV) infusion of the peptide at a small dose of $5{\mu}g/0.2ml/hr$ for 98.5 hrs from day 1 to day 5 in sheep not exposed to stress. Feed and water intake during ICV infusion of CRF or UCN decreased significantly compared to those during artificial cerebrospinal fluid (CSF) infusion. NaCl intake during infusion of CRF or UCN was the same as that during CSF infusion. Mean carotid arterial blood pressure (MAP) and heart rate during ICV infusion of CRF or UCN were not significantly different from that during CSF infusion. On the other hand, the plasma glucose concentration during ICV infusion of CRF or UCN tended to be higher than that during CSF infusion. These observations indicate that decreased feed intake induced by CRF and UCN infusion is not mediated by the activation of both the pituitary-adrenal axis and the sympathetic nervous system. The results suggested that brain CRF and UCN act directly in brain mechanisms controlling ingestive behavior to decrease feed and water intake, but do not alter salt intake in sheep.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.669-675
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• 2018

Background/Aims Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) disorders and these patients frequently overlap. Trimebutine has been known to be effective in controlling FD co-existing diarrhea-dominant IBS, however its effect on overlap syndrome (OS) patients has not been reported. Therefore, we investigated the effect of trimebutine on the model of OS in guinea pigs. Methods Male guinea pigs were used to evaluate the effects of trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated for 1 hour. The next treatment of $10{\mu}g/kg$ of CRF was intraperitoneally injected and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic transits were assessed after the same order and concentrations of trimebutine and CRF treatment by fecal pellet output assay. Results Different concentrations (1, 3, and $10{\mu}g/kg$) of rat/human CRF peptides was tested to establish the OS model in guinea pigs. CRF $10{\mu}g/kg$ was the most effective dose in the experimental OS model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly reversed the upper and lower GI transit of CRF induced OS model. Trimebutine significantly increased upper GI transit while it reduced fecal pellet output in the CRF induced OS model. Conclusions Trimebutine has been demonstrated to be effective on both upper and lower GI motor function in peripheral CRF induced OS model. Therefore, trimebutine might be an effective drug for the treatment of OS between FD and IBS patients.