• 대한본초학회지
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• 제25권4호
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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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• 제13권11호
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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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• 제24권4호
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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.

• 생물정신의학
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• 제10권1호
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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.

• 대한화장품학회지
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• 제43권4호
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• pp.281-287
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• 2017

피부에 가해지는 스트레스는 헤어조절 및 사이클에 직 간접적으로 중요한 영향을 미친다고 알려져 있다. 특히, 모근세포는 스트레스에 의한 부신피질관련호르몬과 세포손상 및 사멸과 밀접한 관련이 있다고 보고되고 있지만, 현재까지 실험적으로 입증된 사실은 매우 제한되어 있다. 보고에 의하면, 부신피질자극호르몬방출인자가 증가되면 모근세포의 마이토콘드리아 활성을 저해하여 초기단계의 세포사멸을 가져올 수 있다고 임상학적으로 보고된바가 있다. 특히 아토피 피부염으로 인한 스트레스는 부신피질자극호르몬방출인자와 부신피질관련 호르몬의 양을 증가시키며, 이는 모발의 outer epithelial sheath에 영향을 준다고 알려져 있으며, 이러한 스트레스의 변화는 마이토콘드리아 손상을 초래하여 초기단계세포손상을 준다고 한다. 따라서 본 연구는 아토피피부염스트레스가 피부의 모근세포에 주는 영향에 대하여 연구를 하였는데, 이에 대한 연구는 현재까지 전무한 실정이다. 우리는 NC/Nga 마우스에 2,4-dinitrochlorobenzene (DNCB)로 아토피피부염을 유발 후, 피부 스트레스 생성에 의한 초기단계 세포손상을 스트레스관련 인자, 부신피질자극호르몬방출인자 및 그 관련 인자, annexin V 및 마이토콘드리아 반응을 이용하여 연구하였다. 그 결과, 아토피피부염에 의한 스트레스는 체내의 부신피질 자극호르몬방출인자 및 관련인자의 활성을 증가시킬 뿐 아니라, 모근세포에 영향을 주어 초기단계세포사멸을 초래하는 것으로 나타났다. 이는 아토피피부염관련 헤어손상을 일으킨다는 중요한 연구결과를 보고하는 바이며, 부신피질자극호르몬 조절관련 의약품 및 화장품 등과 같은 보조적 요법이 필요함을 제안한다.

• Animal Bioscience
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• 제35권8호
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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.

• 통합자연과학논문집
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• 제11권1호
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• pp.19-24
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• 2018

CRFR is involved in the pathophysiology of various disorders including depression, stress, anxiety, post-traumatic stress disorder, and addiction. The discovery of novel and structurally diverse CRF1 receptor inhibitors becomes essential. In this study, we have performed molecular docking of CRF1R with the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolines as CRF1R inhibitors. The antagonist molecules were optimized and docked into the binding site of the receptor. On analysing the docked complexes we have identified that the residues HIS214, THR215, ARG227, ARG1008, LYS1060 and ASP1061 are important in forming hydrogen bond with the inhibitors. Further studies on these residues could reveal important structural features required for the formation of CRF1R-inhibitor complex and thus in the discovery of novel and potent inhibitors.

• 대한한의학방제학회지
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• 제18권1호
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• pp.155-167
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• 2010

Objectives : In order to investigate the antidepressant effects of Forsythiae Fructus(FF), we performed the Forced Swimming Test(FST). Also the expressions of corticotropin-releasing factor (CRF), c-Fos and tyrosine hydroxylase(TH) were measured by immunohistochemical method at paraventricular nucleus(PVN), ventral tegmental area(VTA) and locus coeruleus(LC). Methods : Spraque-Dawley rats were administered FF extract(100 mg/kg, 400 mg/kg) intragastrically three times prior to the FST. Results : The duration of immobility in the FST was significantly decreased in the FF 100 mg/kg, 400 mg/kg groups(p<0.05). The expression of CRF was significantly reduced in the FF 100 mg/kg and 400 mg/kg groups(p<0.001). c-Fos expression was significantly decreased at PVN in the FF 100 mg/kg group(p=0.069). TH expression at VTA was significantly increased in the FF 100 mg/kg and 400 mg/kg groups(p<0.05). TH expression at LC was not significantly changed(p=0.346). Conclusion : According to the results, it can be suggested that Forsythiae Fructus has antidepressant effect via the decreased immobility through the reduction of CRF and c-Fos expression at PVN.

• Journal of Acupuncture Research
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• 제20권6호
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• pp.89-102
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• 2003

Objective: The expression of CRF(corticotropin releasing factor), CRF-R(receptor) and CRF-BP(binding protein) in CNS neurons projecting to the stomach and ST36 using the pseudorabies virus in the rat was investigated. Methods: After survival times of 5 days following injection of PRV-Ba-Gal, The thirty rats were perfused, and their brain were frozen sectioned($30{\mu}m$). These sections were stained by PRV-Ba-Gal histochemical staining method and(or) CRF, CRF-R and CRF-BP immunohistochemical method. The common expressed areas of the brain projecting to the stomach and zusanli(ST36) following injection of PRV-Ba-Gal were observed with light microscope. Results: 1) The dense accumulation of CRF-immunoreactive terminals is seen in the area postrema, n. tractus solitarius, external zone of the median eminence, with some immunoreactive CRF also present in the internal zone. 2) Aggregates of CRF-R immunoreactive perikarya are found in area postrema, n. tractus solitarius, lateral reticular n., gigantocellular reticular n., locus coeruleues, paraventricular n. of hypothalamus, median eminence, preoptic n., arcuate n. and hind limb area of cerebral cortex. 3) Aggregates of CRF-BP immunoreactive perikarya are found in area postrema, n. tractus solitarius, lateral reticular nucleus, gigantocellular reticular n., locus coeruleues, paraventricular n. of hypothalamus, median eminence and arcuate n.. Conclusions : These results suggest that PRV-Ba-Gal labeled areas projecting to stomach and ST36 may be related to the central autonomic pathways. A part of CNS neurons projecting to the stomach and ST36 were related to expression of CRF, CRF-R and CRF-BP related to the stress in central autonomic center.

• 대한한방부인과학회지
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• 제27권4호
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• pp.25-42
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• 2014

Objectives: To observe the effects of Herb medication on Polycystic Ovary (PCO) in rats. Methods: Riss (Research Information Sharing Service) was searched for Oriental medicine about PCO on 2000~2014. So, Experimental studies using PCO model induced by Estradiol Valerate (EV) was selected to analyze how effects they were. Consequently, 10 studies published on 2000~2014 were selected to analyze about weight of model and both ovaries, the number aries, the number of follicle and corpus of follicle and corpus luteum, the level of serum Androstenedione (ADD) and total estrogen, the level of Nerve Growth Factor (NGF) and Corticotropin Releasing Factor (CRF), the crossover rate and the number of implantation. Results: Among them, there was significantly difference between treatment group and control group in weight of both ovaries, the number of follicle and corpora lutea, the crossover rate and the number of implantation. Conclusions: The effects of Herb medication was observed on making weight of ovaries with PCO to promote. The study about effect of Herb medication on NGF and CRF with PCOS had to be conducted. The further research have to focus on treatment of subfertility and infertility, that is field showing the advantage of Oriental medicine.