• Archives of Pharmacal Research
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• v.22 no.6
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• pp.549-553
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• 1999

The antipruritic effect of DA-5018m a capsaicin derivative, was examined in mice. Male ICR mice were topically pretreated with Zostrix-HP (0.075% capsaicin cream), 0.1%, 0.3% DA-5018 cream or cream base (control) twice daily for 4 days. One hour after the last application, itch was induced either by compound 48/80 ($50{\mu}g$, s.c.) or leukotriene B4 (0.03 nmol, i.d.) injection into the rostral back of the animals, and the number of scratches made by the animals at the injection site was counted for 60 min post-injection. DA-5018 cream (both 0.1 and 0.3%) significantly inhibited compound 48/80-induced scratching when compared with the cream base control (p<0.01), which Zostrix-HP showed minimal inhibition of the scratching behavior. In leukotriene B4-induced itch model, Zostrix-HP and 0.3% DA-5018 cram significantly inhibited the scratching during the first 10-min period (p<0.01). The results suggest that DA-5018 cream can be used as an antipruritic agent and warrant clinical evaluation.

• The Journal of Korean Medicine
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• v.28 no.3 s.71
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• pp.165-172
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• 2007

Objectives : To find antipruritic herbal medicines, we screened the water extracts of four herbal medicines which have been frequently prescribed to treat dermatologic diseases in oriental medicine. Methods : Water extracts of Bupleuri Radix, Scutellariae Radix, Cimicifugae Rhizoma and Puerariae Radix were administered at a dose of 300 mg/kg to male ICR mice. 1 hour later, serotonin hydrochloride dissolved in physiologic saline at a concentration of 100 nmol / 50${\mu}{\ell}$ was administered intradermally to the nape of the neck at a dose of 50${\mu}{\ell}$. Then the scratching behavior was observed. Dry skin pruritus was induced with cutaneous application of acetone / ether (1:1) mixture and water (AEW) to the rostral back of male ICR mice, twice a day for 5 days. 14 hours after the last application, the most effective material in the first experiment was administered perorally at doses of 75, 150, 300, 600 and 1200 mg/kg. 1 hour later, the scratching behavior was observed. Results : Water extracts of Puerariae Radix significantly inhibited the serotonin-induced scratching behavior and the mean of scratching bouts was reduced by half compared with the control group. Bupleuri Radix group also showed a 29% decrease in the mean of scratching bouts, but there was no statistical significance. Water extracts of Puerariae Radix also inhibited the AEW-induced scratching behavior, in a dose-dependent manner. The dose of 150 mg/kg showed the highest and statistically significant antipruritic effect. Conclusions : These results suggest that Puerariae Radix and its constituents have antipruritic effect, and are new candidates as antipruritic agents.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.257-264
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• 2015

Background: Korean Red Ginseng-a steamed root of Panax ginseng Meyer-has long been used as a traditional medicine in Asian countries. Its antipruritic effect was recently found, but no molecular mechanisms were revealed. Thus, the current study focused on determining the underlying molecular mechanism of Korean Red Ginseng extract (RGE) against histamine-induced itch at the peripheral sensory neuronal level. Methods: To examine the antipruritic effect of RGE, we performed in vivo scratching behavior test in mice, as well as in vitro calcium imaging and whole-cell patch clamp experiments to elucidate underlying molecular mechanisms. Results: The results of our in vivo study confirmed that RGE indeed has an antipruritic effect on histamine-induced scratching in mice. In addition, RGE showed a significant inhibitory effect on histamine-induced responses in primary cultures of mouse dorsal root ganglia, suggesting that RGE has a direct inhibitory effect on sensory neuronal level. Results of further experiments showed that RGE inhibits histamine-induced responses on cells expressing both histamine receptor subtype 1 and TRPV1 ion channel, indicating that RGE blocks the histamine receptor type 1/TRPV1 pathway in sensory neurons, which is responsible for histamine-dependent itch sensation. Conclusion: The current study found for the first time that RGE effectively blocks histamine-induced itch in peripheral sensory neurons. We believe that the current results will provide an insight on itch transmission and will be helpful in understanding how RGE exerts its antipruritic effects.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.506-512
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• 2012

Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

• 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.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.470-475
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• 2018

Background: It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. Methods: Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 ("MrgprA3/TRPA1"), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. Results: CQ-induced $Ca^{2+}$ influx was strongly inhibited by KRGE ($10{\mu}g/mL$) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced $Ca^{2+}$ influx in MrgprA3/TRPA1. Moreover, both KRGE ($10{\mu}g/mL$) and Rg3 ($100{\mu}M$) suppressed CQ-induced $Ca^{2+}$ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: $274.0{\pm}51.47$ (control) vs. $104.7{\pm}17.39$ (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: $216.8{\pm}33.73$ (control) vs.$115.7{\pm}20.94$ (Rg3)]. Conclusion: The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.

• Natural Product Sciences
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• v.13 no.4
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• pp.373-377
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• 2007

Antiscratching behavioral effects of the water extract of two black colored rice (BCR) varieties [Oryza sativa L. cv. Heugjinjubyeo (HJ) and Josaengheugchalbyeo (JH)], major pigment of which is cyanindin 3-glucoside, were investigated. Orally administered BCRs' extracts exhibited potent inhibitory activity against scratching behaviors which were induced by compound 48/80 and histamine. The inhibitory effect of Josaengheugchalbyeo in vivo and in vitro were more potent than those of Heugjinjubyeo. These finding suggest that black colored rice, especially Josaengheugchalbyeo, may inhibit scratching behaviors and anaphylaxis reaction by stabilizing membrane.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.547-554
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• 2018

Itching is a common clinical symptom of skin disease that significantly affects a patient's quality of life. Transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes and peripheral nerve fibers in skin are involved in the regulation of itching as well as pain. In this study, we investigated whether curcumin, which acts on TRPV1 receptors, affects histamine-induced itching in mice, using behavioral tests and electrophysiological approaches. We found that histamine-induced itching was blocked by topical application of curcumin in a concentration-dependent manner. In ex-vivo recordings, histamine-induced discharges of peripheral nerves were reduced by the application of curcumin, indicating that curcumin acts directly on peripheral nerves. Additionally, curcumin blocked the histamine-induced inward current via activation of TRPV1 (curcumin $IC_{50}=523nM$). However, it did not alter chloroquine-induced itching behavior in mice, which is associated with transient receptor potential ankyrin 1 (TRPA1). Taken together, our results suggest that histamine-induced itching can be blocked by topical application of curcumin through the inhibitory action of curcumin on TRPV1 receptors in peripheral nerves.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.165-173
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• 2014

Objectives : Platycodon Root is frequently used in traditional medicine to treat inflammatory diseases of the throat. The purpose of this study was to characterize the effect of the EtOH extract of fermented Platycodon grandiflorum on the ameliorative effects on the Antipruritic Effect of atopic dermatitis mouse model induced by compound 48/80 and ovalbumin (OVA)-induced allergic responses in mice. Methods : In the present study, we examined the anti allergic effect of Platycodon grandiflorum (PR) and its fermented production (FPR) in several mouse model. We measured acute ear edema in a mouse model caused by TPA and consecutively histological change of Ear tissue was observed by hematoxylin and eosin (H&E) staining. and also Scratching behaviors by compound 48/80 was investigated. The levels of allergic mediators such as immunoglobulin (Ig) E, and anti-oxidant markers such as SOD and MDA in the sera of OVA induced allergic mice were measured by enzyme-linked immunosorbent assay. Results : FPR inhibited compoud 48/80-induced scratching behavior in mice, as well as acetic acid-induced writhing in mice. The anti-scratching behavioral effect of FPR was more potent than PR. FPR extract significantly decreased the serum levels of IgE and MDA compared with those of OVA control group. Conclusions : These results indicate that Anti allergic effect of Platycodon grandiflorum is enhanced by fermentation with Saccharomyces cerevisae and FPR may be useful for protection from the itching reactions, which are IgE-mediated representative skin allergic diseases.