• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.3
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• pp.314-319
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• 2012

Itching is one of the major diagnostic criteria of atopic dermatitis (AD) and one of its most troublesome symptoms that provokes the desire to scratch. Effective control of itching is believed to be one of the basic approaches in controlling AD. The purpose of this study was undertaken to investigate the antipruritic effect of ethanol extracts from Perillae Japonicae Semen leaves (PJSL) and Chaenomelis Fructus (CF) on the scratching behavior induced by pruritogen such as compound 48/80 or substance P in hairless mice. PJSL or CF treatment inhibited histamine release in HMC-1 stimulated compound 48/80 or substance P in a dose-dependant manner. In particularly, co-treatment PJSL ($50{\mu}g/mL$) plus CF ($100{\mu}g/mL$) significantly inhibited histamine release in HMC-1 stimulated compound 48/80 or substance P. PJSL, CF or PJSL plus CF was administered orally for 2 h and then compound 48/80 ($50{\mu}g/site$) or substance P ($100{\mu}g/site$) was injected into rostral back, and scratching of the injected site by the hind paw was counted for 1 h. PJSL or CF administration reduced the scratching behavior induced by compound 48/80 as well as substance P in a dose-dependent manner. Furthermore, co-administration of PJSL and CF markedly suppressed the scratching behavior induced by compound 48/80 as well as substance P. These suppressive effects were synergistically increased by their combination. From the preliminary observations, we considered that ethanol extracts from PJSL and CF could be an effective natural materials for itching treatment.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.246-256
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• 2010

Atopic dermatitis is a common skin disease affecting up to 10% of children and approximately 2% of adults. Atopic dermatitis exhibits four major symptoms, including intense itching, dry skin, redness and exudation. The "itch-scratch-itch" cycle is one of the major features in atopic dermatitis. The pathophysiology and neurobiology of pruritus is unclear. Currently there are no single and universally effective pharmacological antipruritic drugs for treatment of atopic dermatitis. Thus, controlling of itch is a very important unmet need in patients suffering from atopic dermatitis. This article will update progress during the past 10 years of research in the field of pruritus of atopic dermatitis, focusing on aspects of pruritogens (including inflammatory lipids, histamine, serotonin, proteinases, proteinase-activating receptors, neurotransmitters, neuropeptides, and opioid peptides), antipruritic therapies, and emerging new targets. Based on recent progress, researchers expect to identify exciting possibilities for improved treatments and to develop new antipruritic drugs acting through novel targets, such as histamine H4 receptor, gastrin-releasing peptide receptor, MrgprA3, thromboxane A2 receptor and the putative SPC receptor.

• BMB Reports
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• v.49 no.9
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• pp.474-487
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• 2016

Itch is one of the most distressing sensations that substantially impair quality of life. It is a cardinal symptom of many skin diseases and is also caused by a variety of systemic disorders. Unfortunately, currently available itch medications are ineffective in many chronic itch conditions, and they often cause undesirable side effects. To develop novel therapeutic strategies, it is essential to identify primary afferent neurons that selectively respond to itch mediators as well as the central nervous system components that process the sensation of itch and initiate behavioral responses. This review summarizes recent progress in the study of itch, focusing on itch-selective receptors, signaling molecules, neuronal pathways from the primary sensory neurons to the brain, and potential decoding mechanisms based on which itch is distinguished from pain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.83-91
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• 2013

Pruritus is a unpleasant symptom in the skin that provokes the act of or desire to scratch. Mast cells are important effector cells in allergic reactions such as pruritus and inflammation. The purpose of this study was undertaken to investigate the synergic anti-pruritic and anti-inflammatory effects of Scutellariae Radix (SB) plus Flos Loncerae (FL) extracts in rat peritoneal mast cells (RPMCs), pruritogen-induced scratching mice and 2,4-dinitrofluorobenzene (DNFB)-induced allergic mice. We investigated the effect of SB, FL and SB plus FL extracts on the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, and histamine in RPMCs, on the scratching behavior in ICR mice, and skin clinical serverity and inflammatory mediators in DNFB-induced allergic hairless mice. RPMCs stimulated with PMA plus A23187 or compound 48/80 significantly increased TNF-${\alpha}$, IL-$1{\beta}$ or histamine production compared with media control. However, TNF-${\alpha}$ IL-$1{\beta}$ or histamine levels increased by PMA plus A23187 or compound 48/80 treatment were significantly inhibited by SB, FL in a dose-dependent manner. Especially, SB plus FL pretreatment had a synergic inhibitory effects on stimulator-induced cytokines (TNF-${\alpha}$ and IL-$1{\beta}$) and histamine production. Moreover, SB plus FL administration had a synergic inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin, substance P) in ICR mice. Furthermore, SB plus FL administration had a synergic inhibitory effects on skin damage, inflammatory mediators, leukocyte and mast cell infiltration induced by DNFB in hairless mice. These results suggest that SB plus FL administration has a potential use as a medicinal plant for treatment against itching and inflammation-related skin disease.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.316-320
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• 2010

Pruritus is one of major symptoms in atopic dermatis. The pathophysiological mechanism of pruritus is unclear. The search for pruritogen is important in elucidating the pathophysiological mechanism of pruritus in atopic dermatitis. Glucosylsphingosine (Gsp) is upregulated in the strateum corneum of atopic dermatitis patients. We investigated to determine whether Gsp induces itch-scratch responses (ISRs) in mice. Intradermal administration of Gsp induces ISRs. Gsp dose-dependently induced scratching response at 50-500 nmol/site range. Pretreatment with naltrexone, an opioid $\mu$ receptor antagonist, and capsaicin, a TrpV1 receptor agonist, inhibited Gsp-induced ISRs. Additionally, Gsp-induced ISRs were also suppressed by cyproheptadine, an antagonist of serotonin receptor. These findings suggest that Gsp-induced scratching might be at least partly mediated by capsaicin-sensitive primary afferents, and the opioids receptor systems might be involved in transmission of itch signaling in the central nervous system. Furthermore, our findings suggest that Gsp-induced ISRs may be attributable to the serotonin-mediated pathways and Gsp is not any more one of byproducts of abnormal skin barrier but can lead to induce pruritus, one of typical symptoms of atopic dermatitis.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.497-503
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• 2017

Recent reports claimed that glucosylsphingosine (GS) is highly accumulated and specifically evoking itch-scratch responses in the skins of atopic dermatitis (AD) patients. However, it was unclear how GS can trigger itch-scratch responses, since there were no known molecular singling pathways revealed yet. In the present study, it was verified for the first time that GS can activate mouse serotonin receptor 2a (mHtr2a) and 2b (mHtr2b), but not 2c (mHtr2c) that are expressed in HEK293T cells. Specifically, effects of GS on all mouse serotonin receptor 2 subfamily were evaluated by calcium imaging techniques. The GS-induced intracellular calcium increase was dose-dependent, and antagonists such as ketanserin (Htr2a antagonist) and RS-127445 (Htr2b antagonist) significantly blocked the GS-induced responses. Moreover, the proposed GS-induced responses appear to be mediated by phospholipase C (PLC), since pretreatment of a PLC inhibitor U-73122 abolished the GS-induced responses. Additionally, the GS-induced calcium influx is probably mediated by endogenous TRPC ion channels in HEK293T cells, since pretreatment of SKF-96365, an inhibitor for TRPC, significantly suppressed GS-induced response. In conclusion, the present study revealed for the first time that GS can stimulate mHtr2a and mHtr2b to induce calcium influx, by utilizing PLC-dependent pathway afterwards. Considering that GS is regarded as a pruritogen in AD, the present study implicates a novel GS-induced itch signaling pathway.

• Korean Journal of Pharmacognosy
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• v.44 no.1
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• pp.60-69
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• 2013

The worldwide prevalence and severity of allergic diseases including atopic and contact dermatitis has increased dramatically over the past decade, especially in developed countries. Mast cells are important effector cells in allergic reactions. The purpose of this study was undertaken to investigate the anti-allergic and anti-pruritic effects of Diospyros lotus leaf extract (DLE). DLE was prepared by extracting with distilled water. In the present study, we investigated the effect of DLE on the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\alpha}$) and histamine in rat peritoneal mast cells (RPMCs), and on the skin lesion, leukocyte infiltration and scratching behavior in mice. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 significantly increased TNF-${\alpha}$ and IL-$1{\beta}$ production compared with media control. However, TNF-${\alpha}$ and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by DLE in a dose-dependent manner. DLE also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, DLE administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine) in ICR mice. Furthermore, DLE inhibited the skin lesions, inflammatory and mast cells in hairless mice sensitized by 2,4-dinitrofluorobenzene (DNFB). DLE administration reduced the IL-4 and IgE production induced by DNFB sensitization in hairless mice. These results suggest that DLE has a potential use as a herb medicine for treatment against allergy and pruritus-related disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.902-907
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• 2012

The worldwide prevalence and severity of allergic diseases including atopic dermatitis and asthma has increased dramatically over the past decade, especially in developed countries. Mast cells are important effector cells in allergic reactions. The purpose of this study was undertaken to investigate the anti-allergic activities of the extract of Duchesnea chrysantha (DCE). DCE was prepared by extracting with 80% ethanol. In the present study, we investigate the effect of DCE on the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and histamine in the human mast cell line (HMC-1 cells) and on the scratching behavior in hairless mice. Various concentrations of DCE were treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. PMA plus A23187 significantly increased TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-8 production compared with media control. We also show that the increased cytokines such as TNF-${\alpha}$ IL-$1{\beta}$, IL-6, and IL-8 were significantly inhibited by DCE in a dose-dependent manner. Moreover, DCE inhibited the histamine release from HMC-1 cells stimulated by compound 48/80, which promotes histamine release. Futhermore, the administration of DCE reduced the scratching behavior induced by pruritogen (compound 48/80 or histamine) in hairless mice. These results suggest that DCE has a potential use as a medicinal plant for treatment against allergy-related disease.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.79-85
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• 2014

Objectives : In this study, we attempted to evaluate the effects of Careswell on human mast cell-mediated allergy inflammation in vitro and pruritogen-induced scratching behavior in vivo. Method : The Careswell was extract by distilled water. The anti-itching effects of Careswell were investigated on the compound 48/80 ($50{\mu}g/kg$) or histamine ($100{\mu}g/kg$) induced scratching behavior male ICR mice for 30 min by an observer blind. Terfenadine (10 mg/kg) was used as a positive control drug. The cell toxicity of Careswell was determined by 3-(4,5-dimethylthiazole-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The regulatory effect of Careswell on interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ levels was determined by enzyme-linked immunosorbent assay (ELISA) in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) stimulated human mast cells (HMC-1). Also, we evaluated the effect of Careswell on PMACI induced the activation of Nuclear factor-kappa B (NF-${\kappa}B$) into nucleus by Western blot analysis. Result : The results revealed that the oral administration of Careswell (200 mg/kg, p.o.) attenuated the compound 48/80 or histamine-induced scratching behavior in mice. We showed that Careswell significantly reduced the PMACI-induced the production of IL-6 (0.5-1 mg/ml) and TNF-${\alpha}$ (0.1-1 mg/ml). Additionally, Careswell significantly inhibited the activation of NF-${\kappa}B$ in PMACI-stimulated HMC-1. Conclusion : Collectively, the findings of this study provide us with a novel insight into the pharmacological actions of Careswell as a potential molecule for use in the treatment of allergic inflammation diseases.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.93-100
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• 2013

Objectives : This study was to evaluate the anti-inflammatory and anti-pruritic effects of WSY-1075 composited with Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Ginseng Radix, Cervi parvum Cornu and Cinnamomi Cortex in rat peritoneal mast cells (RPMCs) and scratching mouse model. Methods : WSY-1075 was prepared by extracting with 30% ethanol. In the present study, we investigated the effect of WSY-1075 on the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and histamine in rat peritoneal mast cells (RPMCs) activated with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187, and on the scratching behavior in mice treated with pruriogens. Results : WSY-1075 was not cytotoxic effect in used all concentration. PMA plus A23187 treatment significantly increased TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production compared with media control in RPMCs. However, TNF-${\alpha}$, $IL1{\beta}$ and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by WSY-1075 (200 ${\mu}g/mL$ and 400 ${\mu}g/mL$). WSY-1075 also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, WSY-1075 administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin and substence P) in ICR mice. Conclusion : These results suggest that WSY-1075 administration (200 mg/kg or 400 mg/kg) has the anti-inflammatory and anti-pruritic effects on the activated rat peritoneal mast cell and mouse pruritus. WSY-1075 has a potential use as a composition of medicinal plants for treatment against inflammation- and pruritus-related disease.