• Journal of Ginseng Research
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• 제39권3호
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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.

• 대한화장품학회지
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• 제48권2호
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• pp.113-121
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• 2022

본 연구에서는 발효 과정을 거친 구기자(Lycium chinense) 추출물을 이용하여 항염증 및 항노화 관련 기능성 화장품 소재로서의 활용가치를 검증하고자 nitric oxide (NO) 및 항노화 관련 인자들의 억제 효능을 분석하였다. 물과 70% 에탄올을 용매로 구기자를 추출, 발효, 농축, 동결건조하여 시료를 제조한 다음, MTT assay, NO inhibition activity assay, western blot assay, UPLC 분석을 진행하였다. MTT assay를 통해 세포독성을 측정한 다음, 500 ㎍/mL의 농도를 세포실험에 적용하여 진행하였다. NO 억제 효능의 분석 결과, 발효 구기자 열수 추출물(FLW), 발효 구기자 70% 에탄올 추출물(FLE) 각각 47.96%, 56.71%의 우수한 NO 억제 효능을 나타내었다. Western blot을 통해 주름 관련 단백질인 MMP-1, TRPV-1의 발현양상을 측정한 결과, FLW, FLE 모두 MMP-1, TRPV-1에 대한 발현 억제 효능을 나타내었다. 따라서 발효 구기자 추출물은 항염증 및 항노화 관련 기능성 화장품 소재로서의 높은 활용 가치가 있을 것으로 판단된다.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.83.1-83.1
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• 2006

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of the Korean Society ofApplied Pharmacology
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• pp.105-110
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• 2004

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.95.2-95.2
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• 2006

• International Journal of Oral Biology
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• 제42권1호
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• pp.1-8
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• 2017

In the present study, we investigated the role of peripheral ionotropic receptors in artemin-induced thermal hyperalgesia in the orofacial area. Male Sprague-Dawley rats weighting 230 to 280 g were used in the study. Under anesthesia, a polyethylene tube was implanted in the subcutaneous area of the vibrissa pad, which enabled drug-injection. After subcutaneous injection of artemin, changes in air-puff thresholds and head withdrawal latency time were evaluated. Subcutaneous injection of artemin (0.5 or $1{\mu}g$) produced significant thermal hyperalgesia in a dose-dependent manner. However, subcutaneous injection of artemin showed no effect on air-puff thresholds. IRTX ($4{\mu}g$), a TRPV1 receptor antagonist, D-AP5 (40 or $80{\mu}g$), an NMDA receptor antagonist, or NBQX (20 or $40{\mu}g$), an AMPA receptor antagonist, was injected subcutaneously 10 min prior to the artemin injection. Pretreatment with IRTX and D-AP5 significantly inhibited the artemin-induced thermal hyperalgesia. In contrast, pretreatment with both doses of NBQX showed no effect on artemin-induced thermal hyperalgesia. Moreover, pretreatment with H-89, a PKA inhibitor, and chelerythrine, a PKC inhibitor, decreased the artemin-induced thermal hyperalgesia. These results suggested that artemin-induced thermal hyperalgesia is mediated by the sensitized peripheral TRPV1 and NMDA receptor via activation of protein kinases.

• Animal Bioscience
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• 제36권5호
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• pp.740-752
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• 2023

Objective: Dietary phytase increases bioavailability of phytate-bound phosphorus (P) in pig nutrition affecting dietary calcium (Ca) to P ratio, intestinal uptake, and systemic utilization of both minerals, which may contribute to improper bone mineralization. We used phytase to assess long-term effects of two dietary available P (aP) levels using a one-phase feeding system on gene expression related to Ca and P homeostasis along the intestinal tract and in the kidney, short-chain fatty acids in stomach, cecum, and colon, serum, and bone parameters in growing gilts and barrows. Methods: Growing pigs (37.9±6.2 kg) had either free access to a diet without (Con; 75 gilts and 69 barrows) or with phytase (650 phytase units; n = 72/diet) for 56 days. Samples of blood, duodenal, jejunal, ileal, cecal, and colonic mucosa and digesta, kidney, and metacarpal bones were collected from 24 pigs (6 gilts and 6 barrows per diet). Results: Phytase decreased daily feed intake and average daily gain, whereas aP intake increased with phytase versus Con diet (p<0.05). Gilts had higher colonic expression of TRPV5, CDH1, CLDN4, ZO1, and OCLN and renal expression of TRPV5 and SLC34A3 compared to barrows (p<0.05). Phytase increased duodenal expression of TRPV5, TRPV6, CALB1, PMCA1b, CDH1, CLDN4, ZO1, and OCLN compared to Con diet (p<0.05). Furthermore, phytase increased expression of SCL34A2 in cecum and of FGF23 and CLDN4 in colon compared to Con diet (p<0.05). Alongside, phytase decreased gastric propionate, cecal valerate, and colonic caproate versus Con diet (p<0.05). Phytase reduced cortical wall thickness and index of metacarpal bones (p<0.05). Conclusion: Gene expression results suggested an intestinal adaptation to increased dietary aP amount by increasing duodenal trans- and paracellular Ca absorption to balance the systemically available Ca and P levels, whereas no adaption of relevant gene expression in kidney occurred. Greater average daily gain in barrows related to higher feed intake.

• Molecules and Cells
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• 제27권4호
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• pp.417-422
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• 2009

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.183-188
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• 2007

Using BHK cells with stable expression of cardiac $Na^+/Ca^{2+}$ exchanger(BHK-NCX1), reverse mode(i.e. $Ca^{2+}$ influx mode) of NCX1 current was recorded by whole-cell patch clamp. Repeated stimulation of reverse NCX1 produced a cytosolic $Ca^{2+}$-dependent long-term inactivation of the exchanger activity. The degrees of inactivation correlated with NCX1 densities of the cells and were attenuated by reduced $Ca^{2+}$ influx via the reverse exchanger. The inactivation of NCX1 was attenuated by(i) inhibition of $Ca^{2+}$ influx with reduced extracellular $Ca^{2+}$, (ii) treatment with NCX1 blocker($Na^{2+}$), and (iii) increase of cytoplasmic $Ca^{2+}$ buffer(EGTA). In BHK-NCX1 cells transiently expressing TRPV1 channels, $Ca^{2+}$ influx elicited by capsaicin produced a marked inactivation of NCX1. We suggest that cytoplasmic $Ca^{2+}$ has a dual effect on NCX1 activities, and that allosteric $Ca^{2+}$ activation of NCX1 can be opposed by the $Ca^{2+}$-dependent long-term inactivation in intact cells.

• Annals of dermatology
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• 제30권6호
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• pp.653-661
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• 2018

Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.